Neurophysiology: Hodgkin and Huxley Experiments

Action Potential Overview

• Action potentials are crucial for rapid information transport in axons and muscles.
• They are generated by the opening and closing of voltage-gated ion channels, leading to a rapid change in membrane potential.
• Action potentials are all-or-none events, meaning they either occur completely or not at all, once triggered.

Mechanisms of Action Potential

• Frequency coding: The intensity of a signal is represented by the frequency of action potentials.
• Recruitment: The number of axons firing action potentials represents a stronger signal.
• Place code: The identity of the axon carrying the action potential indicates the origin of the signal.
• Voltage-gated Na+, K+, and Ca++ channels generate the action potential's rapid and faithful propagation.

Types of Neurons

• Some neurons utilize graded potentials for short-distance signaling. These graded potentials are passive and do not propagate long distances.
• Example: retinal bipolar neurons
• Most neurons use action potentials (nerve impulses), which regenerate and propagate over long distances. These potentials are electrically excitable.
• Example: lower motor neurons in the spinal cord

Action Potential Phases

• Resting phase: The membrane potential is negative (approximately -70 mV). Specific ion channels are open at this point in time.
• Rising phase: The membrane potential rapidly increases toward a positive value. This is driven by the influx of Na+ ions across the membrane.
• Overshoot: The membrane potential briefly becomes positive.
• Falling phase: The membrane potential rapidly returns to a negative value. This is due to the outward movement of K+ ions.
• Undershoot (after-hyperpolarization): The membrane potential dips below the resting potential before gradually returning.

Action Potential Characteristics

• Threshold: The minimum voltage necessary to initiate an action potential.
• Refractory periods: A period during and after an action potential firing where it's difficult or impossible to fire another action potential. This includes the absolute and relative refractory periods.

Investigating the Action Potential

• Factors affecting membrane potential (VM) - P(ION), E(ION)
• Role of squid giant axon in studying action potentials - Easy preparation of the large axon allowed detailed studies of ion currents during the action potential.
• Hodgkin and Huxley - Proposed the voltage-gated ion channels as the basis for generating and propagating action potentials.

Ionic Basis of Action Potential

• Sodium hypothesis: The change in membrane potential(VM) during an action potential is primarily due to changes in Na+ permeability.
• Voltage-gated Na+ channels open and close rapidly in response to depolarization.
• Voltage-gated K+ channels open and close more slowly than Na+ channels as the membrane potential rises and falls.
• Voltage-dependent ion channel gates-m, h, n states represent the different conformational states of the ion channels.
• Structure and function of ion channels: Pore, voltage sensing module, inactivation particle

Passive and Active Membrane Properties

• Passive decay or electrotonic spread occurs in the absence of voltage-dependent ion channel opening.
• Length constant (λ): distance over which an initial voltage change decays to about 37% of its original value, depending on the resistance along and across the membrane.
• Time constant (τ): time (in milliseconds) it takes for a change in membrane potential to decay to about 37% of its original value.

Action Potential Propagation

• Propagation occurs due to passive spread of depolarization and the opening of voltage-gated channels.
• Myelin significantly increases conduction velocity.
• Saltatory conduction: action potential "jumps" between gaps in the myelin sheath (nodes of Ranvier)

Action Potential Velocity Improvement

• Decrease RA (axon resistance): Larger diameter axons have lower resistance, leading to faster conduction.
• Increase RM (membrane resistance): Myelin sheaths increase membrane resistance, increasing length constant, facilitating saltatory conduction.

Synaptic Summation

• The summation of EPSPs (excitatory postsynaptic potentials) and IPSPs (inhibitory postsynaptic potentials) results in a total postsynaptic potential.