INHIBITION BY OMEGA-CONOTOXIN GVIA OF THE CHRONOTROPIC RESPONSES TO SYMPATHETIC AND PARASYMPATHETIC NERVE-STIMULATION IN THE ISOLATED, BLOOD-PERFUSED ATRIUM OF THE DOG

1 We investigated the effects of omega-conotoxin GVIA (omega-CgTX), a blocker of N-type voltage-operated calcium channels, on the chronotrop ic response to stimulation of the intracardiac sympathetic and parasym pathetic nerves in the isolated, blood-perfused right atrium of the do g. 2 Omega-CgTX (0.3-3 nmol) itself did not affect the sinus rate sign ificantly, but it inhibited the negative followed by positive chronotr opic response to simultaneous stimulation of sympathetic and parasympa thetic nerves in a dose-dependent manner. 3 Omega-CgTX at higher doses (1-3 nmol) inhibited the positive response to sympathetic stimulation more strongly than the negative response to parasympathetic stimulati on. Omega-CgTX (3 nmol) abolished the positive chronotropic response t o sympathetic nerve stimulation in the atrium treated with atropine, b ut did not abolish the negative response to selective parasympathetic stimulation. Neither the chronotropic response to noradrenaline nor th e response to acetylcholine was affected by omega-CgTX. 4 These result s indicate that omega-CgTX inhibits not only the response to sympathet ic stimulation but also the response to.parasympathetic stimulation in the dog heart and it inhibits the positive chronotropic response to s ympathetic stimulation more strongly than the negative chronotropic re sponse to parasympathetic stimulation.