Evidence of omega-conotoxin GV1A-sensitive Ca2+ channels in mammalian peripheral nerve terminals

Area of Science:

• Neuropharmacology
• Physiology

Background:

• Voltage-sensitive calcium channels (VSCCs) play critical roles in neurotransmitter release.
• The specific subtypes of VSCCs in mammalian peripheral cholinergic nerve terminals remain incompletely characterized.

Purpose of the Study:

• To investigate the presence and function of omega-conotoxin GV1A (omega-CgTx)-sensitive VSCCs in mammalian peripheral nerves.
• To elucidate the role of these channels in acetylcholine (ACh) release and smooth muscle contraction.

Main Methods:

• Electrophysiological and pharmacological studies were conducted on guinea pig ileum myenteric plexus longitudinal smooth muscle preparation (GPI).
• The effects of omega-CgTx and a 1,4-dihydropyridine antagonist ((-) 202-791) on electrically stimulated twitches, exogenous ACh contractions, and Ca2+-dependent ACh release were assessed.
• Experiments were also performed on a nerve-free rat aorta preparation to differentiate neuronal from smooth muscle channel activity.

Main Results:

• Omega-conotoxin GV1A significantly reduced GPI twitch height and inhibited Ca2+-dependent KCl-stimulated ACh release.
• The 1,4-dihydropyridine antagonist (-) 202-791 inhibited GPI twitch height and exogenous ACh contractions but did not affect ACh release.
• In the rat aorta, omega-CgTx did not affect KCl-induced contractions, while (-) 202-791 did, confirming the specificity of omega-CgTx for neuronal channels.

Conclusions:

• The findings provide strong evidence for the existence of neuronal N-type VSCCs in mammalian peripheral cholinergic nerve terminals.
• These N-type VSCCs are specifically involved in regulating acetylcholine release from these nerve terminals.