N-Type Ca(2+) channels trigger release of excitatory and inhibitory neurotransmitter from nerve endings in canine bronchi.
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.
Asthma Research Group, Smooth Muscle Research Group, and the Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
A M
AM
Johri
L J
LJ
Janssen
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D060848:Agatoxins; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004285:Dogs; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D000109:Acetylcholine; D060848:Agatoxins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D007545:Isoproterenol; D018377:Neurotransmitter Agents; D009543:Nifedipine; D009638:Norepinephrine; D010455:Peptides; D011189:Potassium Chloride; D013111:Spider Venoms; D020866:omega-Conotoxin GVIA; C083855:omega-agatoxin-Aa4b