Calcium channel subtypes for the sympathetic and parasympathetic nerves of guinea‐pig atria

Abstract

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. 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 ω‐conotoxin MVIIC, a blocker of N‐type and OPQ subfamily Ca2+ channels. ω‐Conotoxin GVIA (an N‐type blocker), ω‐agatoxin IVA (a P‐type blocker), nifedipine (an L‐type blocker) and Ni2+ (a T‐ and R‐type blocker) were much less effective. The positive inotropic response resulting from field stimulation of the sympathetic nerves (in the presence of atropine) was abolished by both ω‐conotoxins, while ω‐agatoxin IVA, nifedipine and Ni2+ were ineffective. In the spontaneously beating right atria, the early negative inotropic effect produced by 1,1‐dimethyl‐4‐phenylpiperazinium was abolished by ω‐conotoxin MVIIC; whereas the late positive inotropic effect was partially reduced, but not abolished, by a high concentration of ω‐conotoxin GVIA. None of the peptide toxins affected the chronotropic and the inotropic responses evoked by carbachol and isoprenaline. These results suggested that, under physiological conditions, the release of acetylcholine from paraysmpathetic 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. 1995 British Pharmacological Society