Abstract
We set out to characterize the types of Ca2+ 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 Ca2+ channel blocker (ω-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 Ca2+ channels (ω-agatoxin TK; 10−8 to 10−7 M) or ofl-type Ca2+ 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 ω-conotoxin GVIA (10−7 M) but not by ω-agatoxin TK (10−7 M) or nifedipine (10−7 M); none of these Ca2+ 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 Ca2+ channels, with little or no contribution from L-, P-, Q-, or T-type channels.
Footnotes
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Send reprint requests to: Dr. L. J. Janssen, Department of Medicine, McMaster University (HSC-3U1), Hamilton, Ontario, Canada L8N 3Z5. E-mail: janssenl{at}fhs.csu.mcmaster.ca
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↵1 This work was supported by a grant from the Medical Research Council of Canada, a Career Award (to L.J.J.) from the Pharmaceutical Manufacturers’ Association of Canada (Health Research Foundation), and the Medical Research Council of Canada.
- Abbreviations:
- ASM
- airway smooth muscle
- AgTX
- agatoxin TK
- ω-CTX
- ω-conotoxin GVIA
- EFS
- electrical field stimulation
- ACh
- acetylcholine
- S1
- S2, S3, first, second, and third series of electrical field stimulation pulse trains, respectively
- NE
- norepinephrine
- TTX
- tetrodotoxin
- Received October 22, 1998.
- Accepted April 28, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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