Effects of ω-conotoxin GVIA on cardiac sympathetic nerve function

Abstract

Using a cardiac dialysis technique, the effects of ω-conotoxin GVIA ( N-type Ca 2+ channel blocker) on cardiac sympathetic nerve function was examined in anesthetized cats. Dialysis probes were implanted in the left ventricular wall and the concentration of dialysate norepinephrine (NE) served as an indicator of NE output at cardiac sympathetic nerve endings. Administration of ω-conotoxin GVIA (10 μg/kg i.v.) suppressed dialysate NE responses to the nerve stimulation. The ouabain (1 μM) induced NE increment was less markedly suppressed by ω-conotoxin GVIA. Furthermore, ω-conotoxin GVIA neither influenced neuronal NE uptake nor tyramine induced release of NE from stores. These findings suggest that the neuronal effect of ω-conotoxin GVIA is attributable to a reduction of exocytotic NE release without alterations of neuronal NE uptake or storage. Cardiac dialysis with ω-conotoxin GVIA offers a new approach for the discrimination between Ca 2+ dependent exocytotic and non-exocytotic NE release.