Excitable Cell Physiology

Excitable cell physiology is the study of how specific cells, most notably neurons and muscle cells, generate and respond to electrical signals. This field investigates the establishment of a resting membrane potential across the cell's plasma membrane, which is a voltage difference maintained by ion pumps and channels. Upon stimulation, these cells can undergo a rapid, transient depolarization and repolarization known as an action potential, driven by the controlled flow of ions through voltage-gated channels. These electrical events are the fundamental basis for nerve impulse transmission, muscle contraction, and sensory perception, enabling rapid communication and response within an organism.

  1. Foundations of Membrane Bioelectricity
    1. The Plasma Membrane
      1. Phospholipid Bilayer Structure
        1. Amphipathic Nature of Phospholipids
          1. Hydrophilic Head Groups
            1. Hydrophobic Fatty Acid Tails
              1. Self-Assembly Properties
              2. Fluid Mosaic Model
                1. Membrane Fluidity
                  1. Protein Mobility
                    1. Lipid Rafts
                    2. Membrane Asymmetry
                      1. Leaflet Composition Differences
                        1. Maintenance of Asymmetry
                          1. Functional Significance
                        2. Membrane Proteins
                          1. Integral Membrane Proteins
                            1. Transmembrane Domains
                              1. Alpha-Helical Structure
                                1. Membrane Spanning Regions
                                2. Peripheral Membrane Proteins
                                  1. Surface Association
                                    1. Lipid Anchoring
                                      1. Protein-Protein Interactions
                                      2. Ion Channels
                                        1. Structural Features
                                          1. Pore Formation
                                            1. Selectivity Filter
                                              1. Channel Architecture
                                              2. Ion Selectivity
                                                1. Size Exclusion
                                                  1. Charge Selectivity
                                                    1. Dehydration Energy
                                                    2. Gating Mechanisms
                                                      1. Voltage-Gated Channels
                                                        1. Voltage Sensor Domain
                                                          1. Conformational Changes
                                                            1. Activation and Inactivation Gates
                                                            2. Ligand-Gated Channels
                                                              1. Binding Site Location
                                                                1. Allosteric Mechanisms
                                                                  1. Cooperativity
                                                                  2. Mechanically-Gated Channels
                                                                    1. Force Transmission
                                                                      1. Membrane Tension
                                                                        1. Cytoskeletal Coupling
                                                                      2. Channel Kinetics
                                                                        1. Single Channel Behavior
                                                                          1. Open and Closed States
                                                                            1. Transition Rates
                                                                            2. Channelopathies
                                                                              1. Genetic Basis
                                                                                1. Loss of Function Mutations
                                                                                  1. Gain of Function Mutations
                                                                                    1. Clinical Phenotypes
                                                                                  2. Transporters and Pumps
                                                                                    1. Facilitated Diffusion Transporters
                                                                                      1. Uniporters
                                                                                        1. Conformational Change Mechanism
                                                                                          1. Saturation Kinetics
                                                                                          2. Primary Active Transporters
                                                                                            1. ATP-Dependent Mechanisms
                                                                                              1. Sodium-Potassium Pump
                                                                                                1. Alpha and Beta Subunits
                                                                                                  1. Three Sodium Out, Two Potassium In
                                                                                                    1. Electrogenic Nature
                                                                                                      1. Ouabain Sensitivity
                                                                                                      2. Calcium Pump
                                                                                                        1. SERCA and PMCA Types
                                                                                                          1. Calcium Binding Sites
                                                                                                            1. ATP Hydrolysis Coupling
                                                                                                            2. Proton Pumps
                                                                                                              1. Gastric H+/K+ ATPase
                                                                                                                1. Vacuolar H+ ATPase
                                                                                                              2. Secondary Active Transporters
                                                                                                                1. Gradient-Driven Transport
                                                                                                                  1. Symporters
                                                                                                                    1. Sodium-Glucose Cotransporter
                                                                                                                      1. Sodium-Amino Acid Cotransporters
                                                                                                                      2. Antiporters
                                                                                                                        1. Sodium-Calcium Exchanger
                                                                                                                          1. Sodium-Hydrogen Exchanger
                                                                                                                      3. Receptors
                                                                                                                        1. Ionotropic Receptors
                                                                                                                          1. Ligand-Gated Ion Channels
                                                                                                                            1. Fast Synaptic Transmission
                                                                                                                              1. Neurotransmitter Binding
                                                                                                                              2. Metabotropic Receptors
                                                                                                                                1. G-Protein Coupled Receptors
                                                                                                                                  1. Second Messenger Systems
                                                                                                                                    1. Modulatory Effects
                                                                                                                              3. Ions and Ion Gradients
                                                                                                                                1. Major Physiological Ions
                                                                                                                                  1. Sodium
                                                                                                                                    1. Intracellular Concentration
                                                                                                                                      1. Extracellular Concentration
                                                                                                                                        1. Concentration Ratio
                                                                                                                                          1. Role in Action Potentials
                                                                                                                                            1. Role in Cotransport
                                                                                                                                            2. Potassium
                                                                                                                                              1. Intracellular Concentration
                                                                                                                                                1. Extracellular Concentration
                                                                                                                                                  1. Concentration Ratio
                                                                                                                                                    1. Role in Resting Membrane Potential
                                                                                                                                                      1. Role in Repolarization
                                                                                                                                                      2. Calcium
                                                                                                                                                        1. Intracellular Concentration
                                                                                                                                                          1. Extracellular Concentration
                                                                                                                                                            1. Concentration Ratio
                                                                                                                                                              1. Role in Signaling
                                                                                                                                                                1. Role in Neurotransmitter Release
                                                                                                                                                                  1. Role in Muscle Contraction
                                                                                                                                                                  2. Chloride
                                                                                                                                                                    1. Intracellular Concentration
                                                                                                                                                                      1. Extracellular Concentration
                                                                                                                                                                        1. Concentration Ratio
                                                                                                                                                                          1. Role in Inhibitory Signaling
                                                                                                                                                                            1. Role in Cell Volume Regulation
                                                                                                                                                                            2. Magnesium
                                                                                                                                                                              1. Intracellular Concentration
                                                                                                                                                                                1. Extracellular Concentration
                                                                                                                                                                                  1. Role in Enzyme Function
                                                                                                                                                                                  2. Phosphate
                                                                                                                                                                                    1. Intracellular Forms
                                                                                                                                                                                      1. Role in Energy Metabolism
                                                                                                                                                                                    2. Concentration Gradients Across the Membrane
                                                                                                                                                                                      1. Establishment of Gradients
                                                                                                                                                                                        1. Active Transport Mechanisms
                                                                                                                                                                                          1. Selective Permeability
                                                                                                                                                                                          2. Maintenance of Gradients
                                                                                                                                                                                            1. Energy Requirements
                                                                                                                                                                                              1. Pump Activity
                                                                                                                                                                                              2. Energetic Cost of Gradient Maintenance
                                                                                                                                                                                                1. ATP Consumption
                                                                                                                                                                                                  1. Metabolic Burden
                                                                                                                                                                                                2. Electrochemical Gradients
                                                                                                                                                                                                  1. Chemical Driving Force
                                                                                                                                                                                                    1. Concentration Differences
                                                                                                                                                                                                      1. Chemical Potential
                                                                                                                                                                                                      2. Electrical Driving Force
                                                                                                                                                                                                        1. Membrane Potential
                                                                                                                                                                                                          1. Electrical Potential Energy
                                                                                                                                                                                                          2. Electrochemical Potential
                                                                                                                                                                                                            1. Combined Chemical and Electrical Forces
                                                                                                                                                                                                              1. Direction of Ion Movement
                                                                                                                                                                                                              2. Equilibrium Potential Concept
                                                                                                                                                                                                                1. Balance of Forces
                                                                                                                                                                                                                  1. No Net Ion Movement
                                                                                                                                                                                                              3. Basic Electrical Concepts
                                                                                                                                                                                                                1. Voltage
                                                                                                                                                                                                                  1. Definition as Potential Difference
                                                                                                                                                                                                                    1. Units of Measurement
                                                                                                                                                                                                                      1. Measurement Techniques
                                                                                                                                                                                                                        1. Resting Potential Values
                                                                                                                                                                                                                          1. Action Potential Amplitude
                                                                                                                                                                                                                          2. Current
                                                                                                                                                                                                                            1. Definition and Units
                                                                                                                                                                                                                              1. Ionic Current
                                                                                                                                                                                                                                1. Direction of Ion Flow
                                                                                                                                                                                                                                  1. Conventional Current Direction
                                                                                                                                                                                                                                    1. Relationship to Ion Movement
                                                                                                                                                                                                                                    2. Resistance and Conductance
                                                                                                                                                                                                                                      1. Ohm's Law Application
                                                                                                                                                                                                                                        1. Membrane Resistance
                                                                                                                                                                                                                                          1. Determinants of Resistance
                                                                                                                                                                                                                                            1. Channel Density Effects
                                                                                                                                                                                                                                            2. Conductance as Reciprocal of Resistance
                                                                                                                                                                                                                                              1. Specific Resistance and Conductance
                                                                                                                                                                                                                                              2. Capacitance
                                                                                                                                                                                                                                                1. Definition and Units
                                                                                                                                                                                                                                                  1. Membrane as a Capacitor
                                                                                                                                                                                                                                                    1. Lipid Bilayer as Dielectric
                                                                                                                                                                                                                                                      1. Charge Separation
                                                                                                                                                                                                                                                      2. Biological Significance
                                                                                                                                                                                                                                                        1. Membrane Charging
                                                                                                                                                                                                                                                          1. Time Constants
                                                                                                                                                                                                                                                      3. Ion Movement Across Membranes
                                                                                                                                                                                                                                                        1. Passive Transport Mechanisms
                                                                                                                                                                                                                                                          1. Simple Diffusion
                                                                                                                                                                                                                                                            1. Lipid Soluble Molecules
                                                                                                                                                                                                                                                              1. Rate Limitations
                                                                                                                                                                                                                                                              2. Facilitated Diffusion
                                                                                                                                                                                                                                                                1. Channel-Mediated Transport
                                                                                                                                                                                                                                                                  1. Carrier-Mediated Transport
                                                                                                                                                                                                                                                                2. Diffusion and Fick's Law
                                                                                                                                                                                                                                                                  1. First Law of Diffusion
                                                                                                                                                                                                                                                                    1. Factors Affecting Diffusion Rate
                                                                                                                                                                                                                                                                      1. Concentration Gradient
                                                                                                                                                                                                                                                                        1. Membrane Area
                                                                                                                                                                                                                                                                          1. Membrane Thickness
                                                                                                                                                                                                                                                                          2. Permeability Coefficient
                                                                                                                                                                                                                                                                            1. Definition and Units
                                                                                                                                                                                                                                                                              1. Factors Determining Permeability
                                                                                                                                                                                                                                                                            2. Electrical Driving Force
                                                                                                                                                                                                                                                                              1. Membrane Potential Influence
                                                                                                                                                                                                                                                                                1. Direction of Ion Movement
                                                                                                                                                                                                                                                                                  1. Electrophoretic Effect
                                                                                                                                                                                                                                                                                  2. The Nernst Equation
                                                                                                                                                                                                                                                                                    1. Theoretical Derivation
                                                                                                                                                                                                                                                                                      1. Assumptions and Limitations
                                                                                                                                                                                                                                                                                        1. Calculating Equilibrium Potential
                                                                                                                                                                                                                                                                                          1. Temperature Dependence
                                                                                                                                                                                                                                                                                            1. Physiological Applications
                                                                                                                                                                                                                                                                                            2. The Goldman-Hodgkin-Katz Equation
                                                                                                                                                                                                                                                                                              1. Constant Field Assumption
                                                                                                                                                                                                                                                                                                1. Multiple Ion Permeabilities
                                                                                                                                                                                                                                                                                                  1. Relative Permeability Ratios
                                                                                                                                                                                                                                                                                                    1. Calculating Membrane Potential
                                                                                                                                                                                                                                                                                                      1. Limitations and Applications
                                                                                                                                                                                                                                                                                                        1. Comparison with Nernst Equation

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                                                                                                                                                                                                                                                                                                    2. The Resting Membrane Potential