CA2-INDUCED DEPRESSION OF VENTRICULAR MYOCYTES( CHANNEL MODULATION ALTERS HALOTHANE)

Purpose: This study examined the direct myocardial depressant effect o f halothane and determined whether an L-type Ca2+ channel agonist and antagonists altered the myocardial depression induced by halothane in cultured rat ventricular myocytes, Methods: Ventricular myocytes were obtained from neonatal rats by enzymatic digestion with collagenase an d then cultured for 6 to 7 days. The myocytes were stabilized in a ser um-free medium, and the spontaneous beating rate and amplitude were me asured, To assess the halothane-induced conformational changes in L-ty pe Ca2+ channel, receptor binding study was performed using a dihydrop yridine derivative, [H-3] PN 200-110, in cardiac membrane preparation. Results: Halothane(1%, 2%, 3%, 4%) decreased the beating rate and amp litude in a concentration-dependent manner (P < 0.05). The myocardial depressant effects of halothane were potentiated by nifedipine or vera pamil (P < 0.05). Bay K 8644, an L-type Ca2+ channel agonist, complete ly prevented the halothane-induced depression in amplitude (P < 0.05), but affected the beating rate less, Adding halothane (2%) decreased ( P < 0.05) the maximum binding site density for [3H] PN 200-110 (from 1 98.6 +/- 23.7 fmol.mg(-1) protein to 115,3 +/- 21.6 fmol.mg(-1) protei n) but did not affect binding affinity (from 0.461 +/- 0.077 nM to 0.3 07 +/- 0.055 nM). Conclusion: The reduction of Ca2+ current via sarcol emmal L-type Ca2+ channel, probably due to conformational changes in d ihydropyridine binding sites, plays an important role in halothane-ind uced myocardial depression in living heart cells.