Selectivity of different calcium antagonists on T- and L-type calcium currents in guinea-pig ventricular myocytes

Both L- and T-type calcium channels are present in the heart. In cardiac myocytes L-type calcium channels are blocked by the classical calcium channel blockers, while T-type calcium channels are thought to be insensitive to these drugs and to be selectively blocked by mibefradil. We aimed to compare the T/L calcium channel blocking selectivity of several calcium channel blockers by evaluating their effects on both components evoked in the same cell from a holding potential corresponding to the normal physiological value (-90 mV). Currents were recorded in single patch-clamped guinea-pig ventricular myocytes, superfused with a Na+- and K+-free solution to abolish overlapping currents. Two dihydropyridines (amlodipine and lacidipine), verapamil diltiazem and mibefradil were tested; for each compound concentrations equieffective on L-type Ca2+ current were used. All calcium channel blockers, at concentrations blocking less than 30% of L-type Ca2+ current, inhibited a significant amount of T-type Ca2+ current, varying from 0.8% (diltiazem) to 28% (mibefradil). We calculated for each compound the T/L ratio. As expected, mibefradil showed the highest T selectivity; lacidipine and diltiazem resulted to be L selective. Verapamil and amlodipine were not selective. Thus, the calcium channel blockers can be differentiated on the basis of their T/L selectivity. (C) 2002 Elsevier Science Ltd. All rights reserved.