The action of calcium channel blockers on recombinant L-type calcium channel α1-subunits

Abstract

1. CHO cells expressing the α(1C-a) subunit (cardiac isoform) and the α(1C-b) subunit (vascular isoform) of the voltage-dependent L-type Ca2+ channel were used to investigate whether tissue selectivity of Ca2+ channel blockers could be related to different affinities for α(1C) isoforms. 2. Inward current evoked by the transfected α1 subunit was recorded by the patch-clamp technique in the whole-cell configuration. 3. Neutral dihydropyridines (nifedipine, nisoldipine, (+)-PN200-110) were more potent inhibitors α(1C-b)-subunit than of α(1C-a)-subunit. This difference was more marked at a holding potential of -100 mV than at -50 mV. SDZ 207-180 (an ionized dihydropyridine) exhibited the same potency on the two isoforms. 4. Pinaverium (ionized non-dihydropyridine derivative) was 2 and 4 fold more potent on α(1C-a) than on α(1C-b) subunit at Vh of -100 mV and -50 mV, respectively. Effects of verapamil were identical on the two isoforms at both voltages. 5. [3H]-(+)-PN 200-110 binding experiments showed that neutral dihydropyridines had a higher affinity for the α(1C-b) than for the α(1C-a) subunit. SDZ 207-180 had the same affinity for the two isoforms and pinaverium had a higher affinity for the α(1C-a) subunit than for the α(1C-b) subunit. 6. These results indicate marked differences among Ca2+ channel blockers in their selectivity for the α(1C-a) and α(1C-b) subunits of the Ca2+ channel.