Neurophysiology: Resting Membrane Potential, Action Potentials, and Synaptic Transmission

Neurophysiology

Resting Membrane Potential (RMP)

The resting membrane potential (RMP) is the electrical potential difference across the plasma membrane of a nonconducting neuron. It is established by the unequal distribution of ions and the selective permeability of the neuronal membrane.

• Extracellular Fluid (ECF): Rich in sodium (Na+), some potassium (K+), and chloride ions (Cl-).

• Intracellular Fluid (ICF): Rich in potassium (K+), large negatively charged proteins, and phosphates.

• Typical RMP Value: -70 mV (inside negative relative to outside); the membrane is said to be polarized.

Ion Channels: Large protein structures in the membrane that allow specific ions to pass. Types include:

• Gated Channels: Open in response to specific stimuli:

  • Chemical stimuli: e.g., neurotransmitters

  • Mechanical stimuli: e.g., pressure

  • Electrical stimuli: changes in membrane potential

Generation of an Action Potential

An action potential (AP) is a rapid sequence of events that reverses the membrane potential and then restores it to RMP. It is the fundamental signal of the nervous system, also called a nerve impulse.

• Depolarization: Opening of Na+ channels causes Na+ influx, making the inside more positive (up to +30 mV).

• Repolarization: Na+ channels close, K+ channels open, and K+ exits the cell, restoring negativity inside.

Key Definitions:

• Sub-threshold stimulus: Weak, opens few Na+ channels, not enough for AP.

• Threshold stimulus: Sufficient to open enough Na+ channels to reach threshold (about -55 mV), triggering an AP.

• All-or-None Principle: If threshold is reached, AP is generated fully; stronger stimuli do not produce larger APs.

• Refractory Period: Time during which a neuron cannot initiate another AP.

Propagation of Action Potentials

Action potentials propagate along axons by two main mechanisms:

• Continuous Conduction: Step-by-step depolarization along unmyelinated axons; slower.

• Saltatory Conduction: AP jumps from one node of Ranvier to the next in myelinated axons; much faster.

Signal Transmission at Synapses

A synapse is the functional junction between two neurons or between a neuron and an effector (muscle or gland). Most synapses in the nervous system are chemical synapses.

Anatomy of a Chemical Synapse

• Presynaptic neuron: Releases neurotransmitter from synaptic vesicles in the axon terminal.

• Synaptic cleft: Small gap between neurons.

• Postsynaptic neuron: Has receptors for neurotransmitter.

Sequence of Events at the Synapse

1. AP arrives at axon terminal of presynaptic neuron.

2. Voltage-gated Ca2+ channels open; Ca2+ enters the terminal.

3. Ca2+ triggers synaptic vesicles to fuse with the membrane and release neurotransmitter (e.g., acetylcholine) into the synaptic cleft by exocytosis.

4. Neurotransmitter diffuses across the cleft and binds to receptors on the postsynaptic membrane.

5. Na+ channels open, Na+ enters the postsynaptic cell, leading toward threshold.

6. K+ channels open, K+ leaves the postsynaptic cell.

7. If threshold is reached, a new AP is generated in the postsynaptic neuron.

8. Acetylcholinesterase (AChE) breaks down acetylcholine, terminating the signal.

Summary Table: Key Events in Synaptic Transmission

Step	Event	Key Molecules
1	AP arrives at axon terminal	Na+, K+
2	Ca2+ influx, vesicle fusion	Ca2+, synaptic vesicles
3	Neurotransmitter release and receptor binding	Acetylcholine, receptors
4	Postsynaptic depolarization, AP generation	Na+, K+
5	Neurotransmitter breakdown and recycling	Acetylcholinesterase, choline, acetate

Key Equations

• Nernst Equation: Used to calculate the equilibrium potential for a particular ion:

$E_{ion} = \frac{RT}{zF} \ln \left( \frac{[ion]_{outside}}{[ion]_{inside}} \right)$

• Goldman-Hodgkin-Katz Equation: Used to calculate the resting membrane potential considering multiple ions:

$V_m = \frac{RT}{F} \ln \left( \frac{P_{K^+}[K^+]_{out} + P_{Na^+}[Na^+]_{out} + P_{Cl^-}[Cl^-]_{in}}{P_{K^+}[K^+]_{in} + P_{Na^+}[Na^+]_{in} + P_{Cl^-}[Cl^-]_{out}} \right)$

Additional info: The above equations are foundational for understanding how ion gradients and membrane permeability establish the RMP and influence action potentials.