Cholinergic Transmission: Site Differences

• Skeletal Muscle

  • Neurotransmitter: Acetylcholine

  • Receptor Type: Nicotinic

  • Sectioning and degeneration of motor and post-ganglionic nerve fibers results in an enhanced post-synaptic responsiveness, denervation hypersensitivity.

• Autonomic Effectors

  • Neurotransmitter: Acetylcholine

  • Receptor type: Muscarinic

  • Effector coupled to receptor by a G protein

  • In smooth muscle and in the cardiac conduction system, intrinsic electrical activity and mechanism activity is present, modifiable by autonomic tone.

    • Activities include propagated slow waves of depolarization. Examples: Intestinal motility and spontaneous depolarizations of cardiac SA nodal pacemakers.

  • Acetylcholine decreases heart rate by decreasing SA nodal pacemaker phase 4 depolarization.

• Autonomic Ganglia

  • Neurotransmitter: Acetylcholine

  • Receptor type: Nicotinic

  • Generally similar to skeletal muscle site: initial depolarization is due to receptor activation. The receptor is a ligand-gated channel.

• Blood vessels

  • Choline ester administration results in blood vessel dilatation as a result of effects on prejunctional inhibitory synapses of sympathetic fibers and inhibitory cholinergic (non-innervated receptors).

  • In isolated blood vessel preparations, acetycholine's vasodilator effects are mediated by activation of muscarinic receptors which cause release of nitric oxide, which produces relaxation.

• Signal Transduction

  • Nicotinic Receptors

    • Ligand-gated ion channels

    • Agonist effects blocked by tubocurarine

    • Receptor activation results in:

      • rapid increases of Na⁺ and Ca²⁺ conductance which causes deplorization then results in excitation

  • Muscarinic Receptors

    • G-protein coupled receptor system

    • Produces slower responses

    • Agonist effects are blocked by atropine

    • At least five receptor subtypes have been described by molecular cloning. Variants have distinct anatomical locations and differing molecular specificities

Category: Pharmacology Notes