Neurophysiology – Ion Channels, Synaptic Transmission & Cholinergic Receptors

Topic focus: neurophysiology—how neurons communicate by changing membrane excitability.
Central idea: ion channels ("gates") open and close to allow specific ions to move, creating changes in membrane voltage that propagate signals.
Source reference from the lecture: textbook pp. 465–467 and the associated outline.
Practical emphasis: all of this material will appear on the next unit exam and the cumulative final.

Cell body (soma): metabolic center containing the nucleus.
Axon: long projection; the action potential travels in one direction away from the soma toward the synapse.
- Emphasized: the impulse does not reverse direction on the axon.
Synapse example used in class: axon terminal of a motor neuron communicating with a skeletal muscle fiber (myofiber)—i.e., a neuromuscular junction (NMJ) from Chapter 10 (muscle tissue).
- Pre-synaptic membrane = neuron terminal.
- Post-synaptic membrane = target cell (muscle, another neuron, gland, etc.).

Synaptic cleft: narrow extracellular space between the two membranes (drawn exaggeratedly large on the board; in reality only a few dozen nanometers).
Neurotransmitter (example: acetylcholine, ACh): chemical messenger released by the presynaptic neuron into the cleft.
- Teacher drew vesicles releasing purple dots = ACh molecules.

The ACh receptor on the muscle membrane is itself a ligand-gated ion channel (also called a nicotinic cholinergic receptor).
- "Ligand gate" logic:
- Lock = channel protein.
- Key = neurotransmitter (ACh in this case).
When ACh binds, the gate specifically opens for sodium (Na⁺).
Extracellular fluid (ECF) is Na⁺-rich; intracellular fluid (ICF) has low Na⁺.
Result of Na⁺ influx: depolarization (inside becomes less negative / more positive).

Resting membrane potential is negative (value not given in lecture, but class convention $\approx -70\;\text{mV}$ ).
Sodium carries a positive charge; entry of Na⁺ makes the internal face of the membrane more positive → depolarization.

Adjacent to the ligand-gated region are voltage-gated Na⁺ channels.
Opening stimulus: a change in membrane voltage (the depolarization caused by Na⁺ from the ligand gate).
Creates a chain reaction: depolarization at one patch opens the next voltage gate → more Na⁺ rushes in → further depolarization downstream (positive feedback).
Trigger zone (axon hillock): region on neuron where voltage-gated channels are first concentrated, ensuring one-way propagation down the axon.

Voltage-gated K⁺ channels are also scattered along the membrane.
- They open in response to depolarization but lag behind Na⁺ channel opening (“me exaggerating, but it’s very, very fast” in comparison to Na⁺ which is even faster).
K⁺ concentration is high inside the cell; when gates open, K⁺ diffuses outward.
Effect: restores (repolarizes) the membrane toward the negative resting value.
If K⁺ outflow overshoots, the membrane becomes more negative than rest → hyperpolarization.

ACh released into cleft.
ACh binds nicotinic receptors → ligand-gated Na⁺ channels open.
Na⁺ influx depolarizes the motor end-plate.
Depolarization opens neighboring voltage-gated Na⁺ channels → action potential spreads bidirectionally in muscle but only one direction along axon due to trigger zone design.
Voltage-gated K⁺ channels open with delay → K⁺ efflux → repolarization and possible hyperpolarization.

Cholinergic = “pertaining to acetylcholine.”
Two receptor families:
1. Nicotinic cholinergic receptors
- Always open Na⁺ channels (ligand-gated).
- Effect: $\text{Na}^+$ influx → depolarization → excitatory on the postsynaptic membrane.
- Found at all skeletal NMJs and many neuron-to-neuron synapses.
1. Muscarinic cholinergic receptors
- Receptor can couple to either:
  a. Na⁺ channels → depolarization (excitatory), or
  b. K⁺ channels → K⁺ efflux → hyperpolarization (inhibitory).
- Thus, muscarinic effects can be excitatory or inhibitory depending on the specific ion channel engaged.
Clinical / pharmacological note: many drugs are classified as “cholinergic,” “anticholinergic,” or more specifically “nicotinic agonist,” “muscarinic antagonist,” etc. Understanding which receptor subtype they target is crucial in nursing and medicine.

Once initiated, the action potential propagates along the membrane in a domino-like fashion due to successive opening of voltage-gated channels.
Positive feedback loop: small depolarization → Na⁺ gate opening → larger depolarization → more gates open.
Structural design (trigger zone, inactivation gates) enforces one-way travel along the axon despite symmetric channel distribution on the muscle membrane.

Builds on Chapter 10 muscular system (motor end plate, NMJ).
Links to earlier cell physiology lessons on membrane potentials.
Foreshadows autonomic pharmacology (adrenergic vs cholinergic) in AMP II and beyond.

Mastery required for safe medication administration (e.g., understanding effects of cholinergic drugs).
Instructor’s caution: “you can’t cut corners”; this information is directly tested.

Textbook pages: 465–467 (approx.).
Resting potential conceptually negative; typical value $\approx -70\;\text{mV}$ (not explicitly stated but implied contextually).
Ion concentration gradients (qualitative):
- ECF: high $\text{Na}^+$ .
- ICF: high $\text{K}^+$ .
Charge changes labelled “positive” or “negative” on the diagram.

Axon, Soma, Synaptic Cleft, Presynaptic/Postsynaptic Membrane, Neurotransmitter, Ligand-Gated Channel, Voltage-Gated Channel, Depolarization, Repolarization, Hyperpolarization, Trigger Zone, Cholinergic, Nicotinic, Muscarinic, Excitatory, Inhibitory.

Memorize the sequence: neurotransmitter binding → ligand gate opens → Na⁺ influx → depolarization → voltage gates open → action potential → K⁺ efflux → repolarization.
Distinguish nicotinic (always excitatory) vs muscarinic (context-dependent).
Understand how ion flow direction and charge determine whether a membrane is excited or inhibited.
Recognize why the neuron’s action potential is unidirectional while a muscle fiber’s can travel both ways from the motor end plate.
Expect exam questions on channel types, ion movement, and receptor pharmacology.