Evans M L, Büsselberg D, Carpenter D O
Wadsworth Center for Laboratories and Research, New York State Department of Health and School of Public Health, Albany 12201-0509.
Neurosci Lett. 1991 Aug 5;129(1):103-6. doi: 10.1016/0304-3940(91)90730-h.
The divalent cation lead (Pb2+) blocks sustained and transient voltage sensitive calcium channel currents of cultured rat dorsal root ganglion cells. The IC50 for inhibition of the total peak current evoked by a step depolarization from -80 to 0 mV was 0.6 microM, compared to an IC50 of 2.2 microM for Cd2+. The current activated by a depolarization from -40 to 0 mV was inhibited by 50% by 1.0 microM Pb2+. Low threshold currents activated by a step from -100 to -30 mV were blocked by Pb2+ at higher concentrations (IC50 = 6 microM). The block progressed in the absence of channel activation and showed little voltage dependence. Peak sodium current was reduced by 6.6% at 1 microM Pb2+ while at 20 microM the peak current was reduced by 40% with marked slowing of the time course of activation. The potassium rectifier current was reduced by 4.1% at 1 microM Pb2+. Thus, Pb2+ selectively blocks calcium currents at concentrations in the range of those causing toxicity in man.
二价阳离子铅(Pb2+)可阻断培养的大鼠背根神经节细胞中持续的和瞬时的电压敏感性钙通道电流。从-80mV阶跃去极化至0mV诱发的总峰值电流受到抑制时,Pb2+的半数抑制浓度(IC50)为0.6μM,相比之下,Cd2+的IC50为2.2μM。从-40mV去极化至0mV激活的电流,在1.0μM Pb2+作用下被抑制50%。从-100mV阶跃至-30mV激活的低阈值电流,在较高浓度(IC50 = 6μM)的Pb2+作用下被阻断。该阻断作用在无通道激活时也会进展,且几乎没有电压依赖性。在1μM Pb2+时,峰值钠电流降低了6.6%,而在20μM时,峰值电流降低了40%,激活的时间进程明显减慢。在1μM Pb2+时,钾整流电流降低了4.1%。因此,Pb2+在导致人体中毒的浓度范围内可选择性地阻断钙电流。