Introduction to the Nervous System and Nervous Tissue: Electrophysiology and Synapses

Electrophysiology of Neurons

The Resting Membrane Potential

The resting membrane potential is a fundamental property of neurons, reflecting the difference in electrical charge across the plasma membrane when the cell is not actively transmitting a signal.

• Ion Distribution: The intracellular fluid (cytosol) contains a high concentration of potassium ions (K+) and negatively charged proteins, while the extracellular fluid contains a high concentration of sodium ions (Na+).

• Charge Difference: The inner portion of the cell is negatively charged compared to the outside. This is primarily due to the continual loss of small numbers of K+ ions through open leak channels, resulting in a net negative charge inside the cell.

• Resting Membrane Potential Value: At rest, the cytosol of a neuron is approximately -70 mV.

Example: If a neuron is at rest, the inside of the cell is about 70 millivolts more negative than the outside.

Ion Channels and Gradients

Ions move across the neuronal membrane through specialized proteins called ion channels, which can be classified based on their gating mechanisms.

• Leak Channels: Always open; do not require a stimulus.

• Gated Channels: Open or close in response to specific stimuli. Types include:

  • Ligand-gated channels: Open in response to a specific chemical (ligand) binding.

  • Voltage-gated channels: Open or close in response to changes in membrane voltage.

  • Mechanically-gated channels: Open or close in response to mechanical stimulation (e.g., stretch, pressure, vibration).

• ATP-consuming Pumps: Ions moving against their electrochemical gradients require energy, provided by pumps such as the sodium-potassium ion pump (Na+/K+ ATPase), which moves two K+ ions into the cell and three Na+ ions out of the cell per cycle.

Equation:

$\text{Na}^+/\text{K}^+ \ \text{ATPase:} \ 3\ \text{Na}^+_{\text{out}} + 2\ \text{K}^+_{\text{in}}$

Local (Graded) Potentials

Local or graded potentials are small, localized changes in membrane potential that occur in response to a stimulus.

• Depolarization: Positive charges enter the cell, making the membrane potential less negative (e.g., from -70 mV to -60 mV).

• Hyperpolarization: Positive charges exit or negative charges enter the cell, making the membrane potential more negative (e.g., from -70 mV to -80 mV).

• Reversibility: Local potentials are reversible; the membrane potential returns to resting value if the stimulus stops.

• Decremental Spread: Local potentials decrease in strength as they spread from the site of stimulation and cannot travel long distances.

• Trigger for Action Potentials: Local potentials can initiate action potentials if they reach threshold at the trigger zone.

Example: A neurotransmitter binding to a dendrite may cause a small depolarization, but unless it reaches threshold, no action potential occurs.

Action Potentials

An action potential is a rapid, uniform depolarization and repolarization of the membrane potential that propagates along the axon, allowing neurons to transmit signals over long distances. Action potentials follow the "all-or-none" principle.

• Events of an Action Potential:

  1. A local potential depolarizes the axolemma of the trigger zone to threshold (about -55 mV).

  2. Voltage-gated Na+ channels open, Na+ enters, and the axon depolarizes rapidly.

  3. At +30 mV, Na+ channels close and voltage-gated K+ channels open, starting repolarization.

  4. Na+ channels return to resting state; repolarization continues as K+ exits.

  5. The axolemma may briefly hyperpolarize before returning to resting membrane potential (-70 mV).

• Refractory Periods:

  • Absolute Refractory Period: No stimulus can trigger another action potential.

  • Relative Refractory Period: Only a strong stimulus can trigger another action potential.

Example: After firing, a neuron cannot immediately fire again due to the refractory period, ensuring one-way propagation of the signal.

Propagation of Action Potentials

Action potentials must be conducted along the axon to transmit information to other cells. The speed and method of propagation depend on axon properties.

• Continuous Propagation: Occurs along unmyelinated axons; the action potential moves in a wave-like fashion.

• Saltatory Propagation: Occurs along myelinated axons; the action potential "jumps" from node to node (nodes of Ranvier), increasing speed.

• Axon Diameter and Speed:

  • Type A fibers: Largest diameter, heavily myelinated, fastest conduction speed.

  • Type B fibers: Intermediate diameter, lightly myelinated, intermediate speed.

  • Type C fibers: Smallest diameter, unmyelinated, slowest speed.

Fiber Type	Diameter	Myelination	Conduction Speed
Type A	Largest	Heavily myelinated	Fastest
Type B	Intermediate	Lightly myelinated	Intermediate
Type C	Smallest	Unmyelinated	Slowest

Neural Synapses

General Terms

A synapse is the junction where a neuron communicates with its target cell, which may be another neuron, a muscle cell, or a gland cell. Synaptic transmission is the process by which signals are transferred across the synapse.

• Presynaptic Neuron: The neuron sending the signal.

• Postsynaptic Neuron: The neuron receiving the signal.

• Electrical Synapse: Direct transfer of ions and electrical signals via gap junctions; found in the brain, cardiac muscle, and visceral smooth muscle.

• Chemical Synapse: Involves the release of neurotransmitters to transmit signals across the synaptic cleft.

Events at a Chemical Synapse

Chemical synapses use neurotransmitters to transmit signals from one neuron to another.

1. An action potential arrives at the axon terminal, triggering voltage-gated Ca2+ channels to open.

2. Influx of Ca2+ causes synaptic vesicles to release neurotransmitter into the synaptic cleft.

3. Neurotransmitters bind to receptors on the postsynaptic cell membrane.

4. Binding of neurotransmitter opens ion channels, leading to a local potential (postsynaptic potential):

   • Excitatory Postsynaptic Potential (EPSP): Local depolarization; brings membrane potential closer to threshold.

   • Inhibitory Postsynaptic Potential (IPSP): Local hyperpolarization; moves membrane potential further from threshold.

   • Summation: Multiple EPSPs and IPSPs can combine to influence whether the postsynaptic neuron reaches threshold and fires an action potential.

5. Termination of synaptic transmission occurs by:

   • Diffusion of neurotransmitter away from the synaptic cleft

   • Enzymatic breakdown of neurotransmitter in the synaptic cleft

   • Reuptake of neurotransmitter into the presynaptic neuron

Example: Acetylcholine is released at the neuromuscular junction, binds to receptors on the muscle cell, and is then broken down by acetylcholinesterase to terminate the signal.

Additional info: The integration of EPSPs and IPSPs at the postsynaptic neuron determines whether an action potential will be generated, a process known as neural integration.