Dihydropyridine-sensitive Ca2+ channel in aneurally cultured human muscles. Relationship between high-affinity binding site and inhibition of calcium uptake.
Dihydropyridine-sensitive Ca2+ channels and the relationship between binding of dihydropyridine derivatives and depolarization-induced Ca2+ uptake have been studied in aneurally cultured human muscle. Analysis of the equilibrium binding of the 1,4-dihydropyridine derivative (+)-PN200-110 revealed a single high-affinity binding site with a Kd of 0.15 +/- 0.05 nM and a Bmax of 87 +/- 12 fmol/mg protein. Inhibition of (+)-[3H]PN200-110 binding by nitrendipine revealed a Ki of 0.8 nM for the nitrendipine-receptor complex. Depolarization of cultured human muscle achieved by elevating the K+ concentration increased the uptake 45Ca2+ which was inhibited by nitrendipine with an IC50 of 1.1 nM. This study demonstrates that aneurally cultured human muscle has dihydropyridine-sensitive voltage-dependent Ca2+ channels which are functional when the fibers are depolarized.
D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D017275:Isradipine; D009132:Muscles / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D010069:Oxadiazoles / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D004095:Dihydropyridines; D007473:Ion Channels; D010069:Oxadiazoles; C038806:1,4-dihydropyridine; D009568:Nitrendipine; D011188:Potassium; D002118:Calcium; D017275:Isradipine