INHIBITION OF MYOCARDIAL L-TYPE AND T-TYPE CA2- POSSIBLE MECHANISM FOR ITS CHRONOTROPIC EFFECT( CURRENTS BY EFONIDIPINE )

Effects of efonidipine, a dihydropyridine phosphonate Ca2+ channel ant agonist, on the guinea-pig heart were compared with those of nifedipin e. In the sino-atrial node, 1 mu M efonidipine produced increase in cy cle length accompanied by prolongation of the phase 4 depolarization w hich was not prominent with 0.1 mu M nifedipine. In ventricular myocyt es, both efonidipine and nifedipine produced inhibition of the L-type Ca2+ current, nifedipine being tenfold more potent than efonidipine. E fonidipine also inhibited the T-type Ca2+ current at higher concentrat ions but nifedipine did not. Both Ca2+ channel antagonists had no or o nly a weak effect an K+ currents. In addition, 40 mu M Ni2+, which sel ectively inhibited the T-type Ca2+ current, had no effect on myocardia l Ca2+ transients and contractile force. In conclusion efonidipine was shown to have inhibitory effects on both L- and T-type Ca2+ currents, which may contribute to its high negative chronotropic potency. (C) 1 998 Elsevier Science B.V. All rights reserved.