Neurophysiology: Membrane Potentials, Action Potentials, and Synaptic Transmission

Neurophysiology: Potentials and Potentials and Potentials

Neuron to Neuron Signals

Neurons communicate through a combination of electrical and chemical signals. Electrical signals transmit information within a neuron, while chemical signals transmit information between neurons at synapses.

• Dendrites receive incoming signals.

• If the combined signals are strong enough, current flows through the soma (cell body).

• The current can trigger an action potential at the axon hillock.

• The action potential travels down the axon to the axon terminal.

• This causes the release of neurotransmitters into the synaptic cleft.

• Neurotransmitters are received by the dendrites of another neuron.

• The process repeats.

Hodgkin and Huxley, 1960s

Alan Hodgkin and Andrew Huxley made foundational discoveries about the electrochemical nature of neuronal firing using the giant axon of the squid.

• Axon firing is electrochemical, involving sodium (Na+) entering the axon and potassium (K+) leaving it.

• Differences in ion concentration across the cell membrane create an electrical charge (potential).

• There are channels in the membrane that allow ions to cross.

• The electrical charge can propagate along the membrane surface.

Electric Signals (Terminology)

All living cells have an electrical charge, with the inside typically more negative than the outside.

• Ions: Electrically charged molecules.

• Anions: Negatively charged ions.

• Cations: Positively charged ions.

• Two forces drive ion movement:

  • Electrostatic pressure: Ions flow towards oppositely charged areas (opposites attract).

  • Diffusion: Ions move from areas of higher to lower concentration (concentration gradient).

Basic Cell Membrane Structure

Cell Membrane and Fluid Compartments

The cell membrane separates the extracellular fluid (outside) from the intracellular fluid (cytoplasm, inside). Concentrations of salts and dissolved substances differ between these compartments.

• Phospholipid bilayer: Forms the basic structure of the membrane, with hydrophilic (water-attracting) heads and hydrophobic (water-repelling) tails.

• Membrane proteins are embedded within or associated with the bilayer.

Transmembrane Proteins

• Channels: Pores that allow specific ions to pass through.

• Gates: Proteins that open or close in response to signals (e.g., voltage, chemicals).

• Pumps: Proteins that actively transport substances across the membrane, often using ATP.

Resting Membrane Potential

Ion Distribution and Resting Potential

At rest, neurons maintain a voltage difference across their membrane, called the resting membrane potential (typically about -65 mV).

• High concentrations of sodium (Na+) and chloride (Cl-) outside the cell; high potassium (K+) inside.

• Negatively charged organic molecules (A-) inside the cell contribute to the negative resting potential.

• Na+ channels are closed at rest; K+ channels are leaky, allowing some K+ to move out.

Maintaining the Resting Membrane

• The sodium-potassium ATPase pump maintains the resting potential by pumping 3 Na+ out for every 2 K+ in.

• This process is energy-intensive, using a significant portion of the body's ATP.

Equation:

$3\,\text{Na}^+_{\text{out}} : 2\,\text{K}^+_{\text{in}}$ (per ATP hydrolyzed)

Action Potentials

Initiation and Phases of the Action Potential

An action potential is a rapid, transient change in membrane potential that propagates along the axon.

• Triggered when the membrane is depolarized to a threshold (usually -40 to -55 mV).

• Depolarization: Voltage-gated Na+ channels open, Na+ rushes in, making the inside more positive.

• Repolarization: Voltage-gated K+ channels open, K+ rushes out, restoring negativity inside.

• Hyperpolarization: Membrane potential becomes more negative than resting before returning to baseline.

Action Potential Phases (see graph):

1. Resting potential (~-65 mV)

2. Threshold reached, Na+ channels open

3. Rapid depolarization (Na+ influx)

4. Peak of action potential

5. Repolarization (K+ efflux)

6. Hyperpolarization and return to resting potential

Action Potentials & Voltage-Gated Sodium Channels

• Voltage-gated Na+ channels open briefly (~1 ms) during depolarization, then inactivate.

• The absolute refractory period is when no new action potential can be triggered.

• The relative refractory period follows, where a stronger stimulus is needed to trigger another action potential.

All-or-Nothing Principle and Rate Law

• Action potentials are all-or-nothing: their size does not diminish as they travel.

• The rate law: stimulus strength is encoded by the frequency of action potentials, not their size.

Action Potential Propagation

Mechanisms of Propagation

• Action potentials are regenerated at each segment of the axon.

• They travel in one direction due to the refractory state of the membrane behind the action potential.

Myelination and Saltatory Conduction

• Myelinated axons conduct action potentials faster via saltatory conduction, where the signal jumps between nodes of Ranvier.

• Unmyelinated axons conduct more slowly, as the action potential must propagate continuously along the membrane.

Conduction Velocity

• Speed of propagation depends on axon diameter and myelination.

• Nodes of Ranvier are gaps in the myelin sheath where action potentials are regenerated.

Postsynaptic Potentials

Excitatory and Inhibitory Postsynaptic Potentials (EPSPs & IPSPs)

Postsynaptic potentials are brief changes in the resting potential of the postsynaptic neuron.

• Excitatory postsynaptic potential (EPSP): Small depolarization, brings cell closer to threshold.

• Inhibitory postsynaptic potential (IPSP): Small hyperpolarization, moves cell further from threshold.

• Balance between EPSPs and IPSPs determines if an action potential is fired.

Summation at the Axon Hillock

• The axon hillock integrates all incoming EPSPs and IPSPs (spatial and temporal summation).

• If the sum is sufficient to reach threshold, an action potential is generated.

Types of Summation

• Spatial summation: Multiple EPSPs/IPSPs from different locations combine.

• Temporal summation: Multiple EPSPs/IPSPs from the same location arrive in quick succession.

Key Table: Ion Concentrations Inside and Outside the Neuron

Ion	Inside (mM)	Outside (mM)
Na+	15	145
K+	140	5
Cl-	10	110
Ca2+	0.0001	2
Proteins (A-)	High	Low

Summary

• Neurons use electrical and chemical signals for communication.

• Resting membrane potential is maintained by ion gradients and the sodium-potassium pump.

• Action potentials are rapid, all-or-nothing events that propagate along axons.

• Myelination increases conduction speed via saltatory conduction.

• Postsynaptic potentials integrate at the axon hillock to determine neuronal firing.