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N-Type Ca(2+) channels trigger release of excitatory and inhibitory neurotransmitter from nerve endings in canine
1Asthma Research Group, Smooth Muscle Research Group, and the Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Abstract:
We set out to characterize the types of Ca(2+) channels that mediate release of the predominant excitatory (acetylcholine) and inhibitory (norepinephrine) neurotransmitters in canine bronchi, using electrically evoked contractions and relaxations, respectively, as indicators of this release. We found that the selective N-type Ca(2+) channel blocker (omega-conotoxin GVIA) eliminated electrically evoked contractions in a dose-dependent fashion (half-maximal inhibition in the presence of 1-5 nM) but had no significant effect on those evoked by exogenously added acetylcholine. Selective blockers of P-type Ca(2+) channels (omega-agatoxin TK; 10(-8) to 10(-7) M) or of L-type Ca(2+) channels (nifedipine; 10(-8) to 10(-6) M) had no significant effect on the responses to neurally released or exogenously added acetylcholine. Likewise, electrically evoked relaxations were blocked by omega-conotoxin GVIA (10(-7) M) but not by omega-agatoxin TK (10(-7) M) or nifedipine (10(-7) M); none of these Ca(2+) channel blockers had a significant inhibitory effect on isoproterenol-triggered relaxations. We conclude that excitatory and inhibitory neurotransmission in canine bronchi is mediated predominantly by N-type Ca(2+) channels, with little or no contribution from L-, P-, Q-, or T-type channels.
Insights
N-type calcium channels mediate both excitatory and inhibitory neurotransmission in canine bronchi. These channels are crucial for acetylcholine and norepinephrine release, influencing airway smooth muscle function.
Area of Science:
- Pharmacology
- Neuroscience
- Respiratory Physiology
Background:
- Airway smooth muscle function is regulated by excitatory and inhibitory neurotransmission.
- Calcium (Ca2+) channels play a critical role in neurotransmitter release.
- Understanding specific Ca2+ channel involvement is key to modulating airway function.
Purpose of the Study:
- To identify the specific types of Ca2+ channels responsible for neurotransmitter release in canine bronchi.
- To differentiate the roles of various Ca2+ channel subtypes in mediating excitatory and inhibitory neurotransmission.
Main Methods:
- Electrically evoked contractions and relaxations in canine bronchi were used to assess neurotransmitter release.
- Selective Ca2+ channel blockers, including omega-conotoxin GVIA (N-type), omega-agatoxin TK (P-type), and nifedipine (L-type), were applied.
- Responses to neurally released and exogenously added neurotransmitters (acetylcholine, norepinephrine, isoproterenol) were measured.
Main Results:
- Selective N-type Ca2+ channel blockade (omega-conotoxin GVIA) dose-dependently inhibited electrically evoked contractions and relaxations.
- N-type Ca2+ channel blockers did not affect responses to exogenously applied acetylcholine or isoproterenol.
- Blockers of L-type and P-type Ca2+ channels had no significant effect on acetylcholine or norepinephrine release.
Conclusions:
- N-type Ca2+ channels are the predominant mediators of both excitatory (acetylcholine) and inhibitory (norepinephrine) neurotransmission in canine bronchi.
- L-type, P-type, Q-type, and T-type Ca2+ channels play minimal roles in these neurotransmission pathways.
- Findings highlight N-type Ca2+ channels as potential therapeutic targets for respiratory conditions affecting airway tone.