Neurotransmission Steps

• Axonal conduction

  • Depolarization of the axonal membrane potential results in an action potential.

  • The upstoke of the action potential is a sodium current flowing through voltage-activated sodium channels

  • As the membrane potential decreases, activation occurs of an outgoing potassium current, which opposes further depolarization and initiates repolarization.

  • Longitudinal spread of local depolarizing sodium currents results in progressive, longitudinal activation of sodium channels and new sites of depolarization. The rate of conduction is dependent on the number and synchrony of sodium channel activation.

  • Number and synchrony of sodium channel activation is membrane potential dependent.

    • As the resting membrane potential decrease (towards 0), fewer sodium channels will be activated by a depolarizing influence and conduction velocity slows.

  • In myelinated fibers, depolarization occurs at the Nodes of Ranvier.

• Synaptic (Junctional) Activity

  • Storage and Release of Neurotransmitter

Small molecule neurotransmitters (e.g. acetylcholine, norepinephrine) are synthesized at axonal terminals and stored in synaptic vesicles.

• Isolated neurotransmitter "quanta", perhaps corresponding to single vesicle neurotransmitter quantity, is randomly released in the basal state. This level of release, generating miniature end-plate potentials, is necessary for resting skeletal muscle tone.

• Action Potentials, promoting calcium influx, induce large, synchronous release of several hundred quanta. Calcium facilitates vesicular membrane-synaptic membrane fusion, resulting in vesicular content discharge into the synaptic cleft.

• Many chemical can inhibit norepinephrine or acetylcholine release through receptor interactions at the appropriate terminal. Examples:

1. Norepinephrine + presynaptic alpha 2-adrenergic receptor (autoreceptor) inhibits norepinephrine release

2. Alpha₂ receptor antagonists increase release of norepinephrine

3. Neurally-mediated acetylcholine release from cholinergic neurons is inhibited by alpha₂-adrenergic receptor agonists

4. Stimulation of presynaptic beta₂ adrenergic receptors increases slightly norepinephrine release

• Termination of Transmitter Action

  • Cholinergic: Termination of action of acetylcholine is acetylcholine hydrolysis. (acetylcholinesterase-catalazed)

    • If acetylcholinesterase is inhibited, the duration of cholinergic effect is increased.

  • Adrenergic: Termination of action of adrenergic neurotransmitters is by reuptake and diffusion away from receptors.

  • Amino Acids: Termination of action of amino-acid neurotransmitters is by active transport into neurons and glia

Category: Pharmacology Notes