Two states of the L-type Ca2+ channel in PC12 cells: different sensitivity to 1,4-dihydropyridines.
A omega-conotoxin-resistant component of high K(+)-induced [Ca2+]i increase in PC12 cells was further divided into two components by the difference in sensitivity to 1,4-dihydropyridines. The initial phase (up to 30s) was several times less sensitive to 1,4-dihydropyridines than the following plateau phase (several minutes). On the other hand, diltiazem blocked both phases with the same potency. Verapamil also was only a little more sensitive to the initial phase. All four 1,4-dihydropyridines tested showed 5-10 times more potent inhibition of (+)-[3H]PN200-110 binding in PC12 cells under the depolarizing (70 mM K+) condition than under the non-depolarizing (5 mM K+) condition. The biphasic blockade of the high K(+)-induced [Ca2+]i rise by 1,4-dihydropyridines appears to reflect their different affinities under depolarizing and non-depolarizing conditions.
Fujimoto
M
M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Mihara
S
S
D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D011188:Potassium