Lacinová L, Klugbauer N, Hofmann F
Institut für Pharmakologie und Toxikologie der Technischen Universität München, Biedersteiner Str. 29, 80802, München, Germany.
Neuropharmacology. 2000 Apr 27;39(7):1254-66. doi: 10.1016/s0028-3908(99)00202-6.
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.
使用全细胞膜片钳记录模式对表达的小鼠T型α(1G)通道的药理学特性进行了表征。以Ba(2+)或Ca(2+)作为载流子。I(Ba)和I(Ca)均被Ni(2+)和Cd(2+)阻断，Ni(2+)的IC(50)值为0.47±0.04 mM，Cd(2+)的IC(50)值为1.13±0.06 mM；Ni(2+)的IC(50)值为162±13 μM，Cd(2+)的IC(50)值为658±23 μM。Ni(2+)而非Cd(2+)改变通道激活的门控特性。Ni(2+)持续加速通道失活，而Cd(2+)仅对I(Ca)有类似作用。α(1G)通道被米贝地尔以剂量和电压依赖性方式强烈阻断。I(Ba)被苯妥英适度阻断(IC(50) 73.9±1.9 μM)，对丙戊酸盐的阻断具有抗性。此外，3 mM乙琥胺在-100和-60 mV的钳制电位下分别阻断20%和35%的I(Ba)，而5 mM阿米洛利抑制I(Ba) 38%并显著减慢电流激活。α(1G)通道不受10 μM河豚毒素的影响。1 μM (+)异搏定和10 μM硝苯地平在-100 mV的钳制电位下分别抑制18%和14%的I(Ba)幅度，在-60 mV的钳制电位下分别抑制23%和29%的I(Ba)幅度。α(1G)电流被1 μM Bay K 8644最小程度激活。
