Role of N-type calcium channels in autonomic neurotransmission in guinea-pig isolated left atria.

Abstract

1. Calcium entry via neuronal calcium channels is essential for the process of neurotransmission. We investigated the calcium channel subtypes involved in the operation of cardiac autonomic neurotransmission by examining the effects of selective calcium channel blockers on the inotropic responses to electrical field stimulation (EFS) of driven (4 Hz) guinea-pig isolated left atria. In this tissue, a previous report (Hong & Chang, 1995) found no evidence for N-type channels involved in the vagal negative inotropic response and only weak involvement in sympathetic responses. 2. The effects of cumulative concentrations of the selective N-type calcium channel blocker, omega-conotoxin GVIA (GVIA; 0.1-10 nM) and the non-selective N-, P/Q-type calcium channel blocker, omega-conotoxin MVIIC (MVIIC; 0.01-10 nM) were examined on the positive (with atropine, 1 microM present) and negative (with propranolol, 1 microM and clonidine, 1 microM present) inotropic responses to EFS (eight trains, each train four pulses per punctate stimulus). 3. GVIA caused complete inhibition of both cardiac vagal and sympathetic inotropic responses to EFS. GVIA was equipotent at inhibiting positive (pIC50 9.29+/-0.08) and negative (pIC50 9.13+/-0.17) inotropic responses. MVIIC also mediated complete inhibition of inotropic responses to EFS and was 160 and 85 fold less potent than GVIA at inhibiting positive (pIC50 7.08+/-0.10) and negative (pIC50 7.20+/-0.14) inotropic responses, respectively. MVIIC was also equipotent at inhibiting both sympathetic and vagal responses. 4. Our data demonstrates that N-type calcium channels account for all the calcium current required for cardiac autonomic neurotransmission in the guinea-pig isolated left atrium.