Regulation of the calcium channel alpha(1G) subunit by divalent cations and organic blockers.
The pharmacological properties of the expressed murine T-type alpha(1G) channel were characterized using the whole cell patch clamp configuration. Ba(2+) or Ca(2+) were used as charge carriers. Both I(Ba) and I(Ca) were blocked by Ni(2+) and Cd(2+) with IC(50) values of 0.47+/-0.04 and 1.13+/-0.06 mM (Ni(2+)) and 162+/-13 and 658+/-23 microM (Cd(2+)), respectively. Ni(2+), but not Cd(2+), modified the gating of channel activation. Ni(2+) consistently accelerated channel deactivation while Cd(2+) had a similar effect only on I(Ca). The alpha(1G) channel was potently blocked by mibefradil in a dose- and voltage-dependent manner. I(Ba) was moderately blocked by phenytoin (IC(50) 73.9+/-1.9 microM) and was resistant to the block by valproate. Also 3 mM ethosuximide blocked 20 and 35% of the I(Ba) at a HP of -100 and -60 mV, respectively, while 5 mM amiloride inhibited I(Ba) by 38% and significantly slowed current activation. The alpha(1G) channel was not affected by 10 microM tetrodotoxin. Both 1 microM (+)isradipine and 10 microM nifedipine inhibited 18 and 14% of I(Ba) amplitude at a HP of -100 mV, and 23% and 29% of I(Ba) amplitude at a HP of -60 mV, respectively. The alpha(1G) current was minimally activated by 1 microM Bay K 8644.
Lacinová
L
L
Institut für Pharmakologie und Toxikologie der Technischen Universität München, Biedersteiner Str. 29, 80802, München, Germany. lacinova@ipt.med.tu-muenchen.de
Klugbauer
N
N
Hofmann
F
F
D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects; D002412:Cations / Q000494:pharmacology; D002460:Cell Line; D004095:Dihydropyridines / Q000494:pharmacology; D004594:Electrophysiology; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020748:Mibefradil / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D014162:Transfection
C121855:CACNA1G protein, human; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D002412:Cations; D004095:Dihydropyridines; D002104:Cadmium; D020748:Mibefradil; D009532:Nickel