Calcium channel subtypes for the sympathetic and parasympathetic nerves of guinea-pig atria.
1. The Ca2+ channel subtypes of the autonomic nerves of guinea-pig atria were elucidated by monitoring the effects of specific Ca2+ channel blockers on the negative and positive inotropic responses associated respectively, with stimulation of the parasympathetic and sympathetic nerves. 2. In left atria paced at 2-4 Hz, the negative inotropic effect induced by field stimulation of parasympathetic nerves (in the presence of propranolol) was abolished by omega-conotoxin MVIIC, a blocker of N-type and OPQ subfamily Ca2+ channels. omega-Conotoxin GVIA (an N-type blocker), omega-agatoxin IVA (a P-type blocker), nifedipine (an L-type blocker) and Ni2+ (a T- and R-type blocker) were much less effective. 3. The positive inotropic response resulting from field stimulation of the sympathetic nerves (in the presence of atropine) was abolished by both omega-conotoxins, while omega-agatoxin IVA, nifedipine and Ni2+ were ineffective. 4. In the spontaneously beating right atria, the early negative inotropic effect produced by 1,1-dimethyl-4-phenylpiperazinium was abolished by omega-conotoxin MVIIC, whereas the late positive inotropic effect was partially reduced, but not abolished, by a high concentration of omega-conotoxin GVIA. 5. None of the peptide toxins affected the chronotropic and the inotropic responses evoked by carbachol and isoprenaline. 6. These results suggested that, under physiological conditions, the release of acetylcholine from parasympathetic nerves is dominated by an OPQ subfamily Ca2+ channel while that of noradrenaline from sympathetic nerves is controlled by an N-type Ca2+ channel. Ligand-induced noradrenaline release appeared to recruit additional type(s) of Ca2+ channel.
Hong
S J
SJ
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Chang
C C
CC
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000145:classification* / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D003864:Depression, Chemical; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000294:innervation*; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002316:Cardiotonic Agents; D005731:Ganglionic Stimulants; D018377:Neurotransmitter Agents; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D004246:Dimethylphenylpiperazinium Iodide; D009532:Nickel; D020866:omega-Conotoxin GVIA; D009543:Nifedipine