Resting potential and action potentials Knowledge-Based Study

Study notes

1. Electrical Charge in Neurons

   In an unstimulated neuron, the cytoplasm adjacent to the inner surface of the plasma membrane carries a net negative electrical charge relative to the extracellular fluid outside. This baseline separation of electric charge across the resting membrane is known as the resting membrane potential, typically measured at approximately -70 mV in mammalian neurons.

   Mechanisms Maintaining the Resting Potential

   • Unequal Ion Distribution: Extracellular fluid contains a high concentration of sodium ions ($Na^+$) and chloride ions ($Cl^-$), whereas intracellular fluid contains a high concentration of potassium ions ($K^+$) and impermeable organic anions (such as proteins and phosphates).
   • Membrane Permeability via Leak Channels: The resting axon membrane contains abundant nongated potassium leak channels and significantly fewer sodium leak channels. Consequently, $K^+$ diffuses out of the cell down its chemical gradient far more readily than $Na^+$ enters, carrying positive charge outward.
   • Sodium-Potassium Exchange Pump: The active $Na^+/K^+$ ATPase continuously transports 3 $Na^+$ ions out of the neuron in exchange for 2 $K^+$ ions brought in, consuming one molecule of ATP per cycle. This electrogenic mechanism maintains the essential chemical concentration gradients.

   Triggering the Impulse

   When an excitatory stimulus reaches a specialized region of the axon called the axon hillock, it induces local mechanical or ligand-gated channels to open, allowing positive ions to enter and partially depolarize the membrane.

   Threshold and the All-or-None Principle

   If the membrane potential depolarizes to a critical level called the threshold potential (typically around -55 mV), it triggers the opening of voltage-gated sodium channels.

   • Positive Feedback Loop: The influx of $Na^+$ down both its concentration and electrical gradients depolarizes the membrane further, prompting additional voltage-gated $Na^+$ channels to open rapidly.
   • All-or-None Response: Any stimulus that brings the axon membrane to threshold produces an action potential of constant amplitude and duration. Subthreshold stimuli fail to generate an action potential entirely, whereas suprathreshold stimuli do not increase action potential size.
   • Peak Depolarization: The membrane potential briefly reverses, rising to approximately +30 mV to +35 mV as $Na^+$ approaches its electrochemical equilibrium.

   Restoring Membrane Polarity

   An action potential lasts only about 1 to 2 milliseconds before the resting polarity is re-established through coordinated channel dynamics.

   Phases of Recovery

   • Inactivation of Sodium Channels: At the peak of depolarization, the inactivation gates of voltage-gated $Na^+$ channels swing shut, terminating the influx of $Na^+$.
   • Voltage-Gated Potassium Activation: Simultaneously, slower voltage-gated $K^+$ channels open fully. Driven by both high intracellular concentration and positive internal charge, $K^+$ rushes out into the extracellular space, causing repolarization.
   • Hyperpolarization (Undershoot): Because voltage-gated $K^+$ channels close gradually, potassium efflux continues slightly beyond the resting potential, driving the voltage down toward approximately -80 mV before returning to baseline with the help of leak channels and the $Na^+/K^+$ pump.

   Refractory Periods

   The absolute refractory period occurs when voltage-gated $Na^+$ channels are inactivated; no stimulus, regardless of strength, can fire a second action potential. The subsequent relative refractory period occurs during hyperpolarization; voltage-gated $Na^+$ channels have reset to their closed-activatable state, but a stronger-than-normal stimulus is required to overcome the heightened potassium conductance.

   Conduction Along the Axon

   An action potential does not travel physically like a fluid; rather, it regenerates sequentially along adjacent patches of the axonal membrane. Local circuit currents from the depolarized region spread intracellularly to adjacent inactive regions, bringing them to threshold.

   Unidirectional Propagation

   The action potential travels in one direction only (from the axon hillock toward the synaptic terminals). The membrane region immediately behind the advancing wave is in its absolute refractory period, preventing backwards propagation.

   Continuous vs. Saltatory Conduction

   • Continuous Conduction: In unmyelinated axons, voltage-gated channels occur along the entire length of the axolemma. Regeneration must occur at every successive membrane patch, resulting in relatively slow conduction speeds.
   • Saltatory Conduction: In myelinated axons, myelin sheaths produced by Schwann cells (PNS) or oligodendrocytes (CNS) provide electrical insulation, preventing charge leakage across the internodes. Voltage-gated channels are clustered almost exclusively at uninsulated gaps called Nodes of Ranvier. The electrical signal spreads rapidly through the cytosol under the myelin sheath, causing the action potential to effectively "jump" from node to node, markedly increasing velocity while conserving metabolic energy.