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

1 CHO cells expressing the α1C‐a subunit (cardiac isoform) and the α1C‐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 α1C 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 of α1C‐b‐subunit than of α1C‐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 α1C‐a than on α1C‐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 α1C‐b than for the α1C‐a subunit. SDZ 207‐180 had the same affinity for the two isoforms and pinaverium had a higher affinity for the α1C‐a subunit than for the α1C‐b subunit. 6 These results indicate marked differences among Ca2+ channel blockers in their selectivity for the α1C‐a and α1C‐b subunits of the Ca2+ channel. British Journal of Pharmacology (1998) 125, 1005–1012; doi:10.1038/sj.bjp.0702162