INHIBITION BY VERAPAMIL AND DILTIAZEM OF AGONIST-STIMULATED CONTRACTILE RESPONSES IN MAMMALIAN VENTRICULAR CARDIOMYOCYTES

Secretin, vasoactive intestinal peptide (VIP) and calcitonin gene-rela ted peptide (CGRP) each exert potent positive contractile responses di rectly in rat ventricular cardiomyocytes. However, the contractile-cou pling mechanisms associated with these responses have not been determi ned. In the present study, the involvement of L-type calcium channels in the contractile responses elicited by each peptide has been investi gated using the selective antagonists at L-type calcium channels, vera pamil and diltiazem. Ventricular cardiomyocytes, isolated from the hea rts of adult rats, were stimulated to contract at 0.5 Hz in the presen ce of CaCl2 (2 mM) and adenosine deaminase (5U/ml). Cardiomyocytes wer e pre-incubated for 3 min prior to stimulation, in the absence of L-ty pe calcium channel antagonist, and in the presence of verapamil (less than or equal to 1 mu M) or diltiazem (less than or equal to 1 mu M). Verapamil (less than or equal to 1 mu M) and diltiazem (less than or e qual to 1 mu M) inhibited the contractile responses elicited by isopre naline (100 nM) and forskolin (40 mu M), used as positive controls, si gnificantly, and in a concentration-dependent manner, but did not inhi bit significantly the contractile response elicited by phenylephrine ( 2 mu M), which was employed as a negative control. Verapamil (less tha n or equal to 1 mu M) and diltiazem (less than or equal to 1 mu M) inh ibited the contractile responses to secretin (20 nM) and VIP (20 nM) s ignificantly, and in a concentration-dependent manner, but did not inh ibit the contractile response to CGRP. These data indicate that the po sitive contractile responses to secretin and VIP in mammalian ventricu lar cardiomyocytes involve the influx of calcium ion via L-type calciu m channels, while the positive contractile response to CGRP does not. (C) 1995 Academic Press Limited