Calcium antagonists High-affinity binding and inhibition of calcium transport in a clonal cell line.
PC12 cells, a clonal rat pheochromocytoma cell line, possess voltage-dependent calcium channels that bind the high affinity dihydropyridine calcium antagonist [3H]nitrendipine and other calcium channel blockers. The binding is temperature-dependent and saturable, and shows no cooperativity. The calcium antagonists inhibit potassium-induced 45Ca uptake into the cells with approximately the same potencies as those needed to inhibit [3H]nitrendipine binding to cell membranes. The affinity of these compounds for the PC12 cell calcium channel is slightly lower than that reported for binding to brain and heart. Potassium-stimulated 45Ca uptake into PC12 cells is rapid, being half-maximal within 30 s at 20 degrees C. Different classes of calcium antagonists seem to block calcium flux at different sites on the calcium channel. A lower limit of the rate of calcium movement through a single channel is given. PC12 cells seem to be a suitable model system for the study of the pharmacology and biochemistry of the voltage-dependent calcium channel.
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D007473:Ion Channels / Q000378:metabolism*; D007700:Kinetics; D009374:Neoplasms, Experimental / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism*; D009568:Nitrendipine; D010673:Pheochromocytoma / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism*; D051381:Rats
D002121:Calcium Channel Blockers; D007473:Ion Channels; D011725:Pyridines; D009568:Nitrendipine; D009543:Nifedipine; D002118:Calcium