Tinker A, Williams A J
Department of Cardiac Medicine, National Heart and Lung Institute, University of London, United Kingdom.
Biophys J. 1995 Jan;68(1):111-20. doi: 10.1016/S0006-3495(95)80165-7.
After incorporation of purified sheep cardiac Ca(2+)-release channels into planar phospholipid bilayers, we have investigated the blocking effects of a series of monovalent (CH3-(CH2)n-1-N+(CH3)3) and divalent ((CH3)3N(+)-(CH2)n-N+(CH3)3) trimethylammonium derivatives under voltage clamp conditions. All the compounds tested produce voltage-dependent block from the cytoplasmic face of the channel. With divalent (Qn) derivatives the effective valence of block decreases with increasing chain length, reaching a plateau with a chain length of n > or = 7. No decline in effective valence is observed with the monovalent (Un) derivatives. A plausible interpretation of this phenomena suggests that for the 90% of the voltage drop measured, the increase in length following the addition of a CH2 in the chain spans 12.7% of the electrical field. Extrapolating this distance to include the remaining 10% suggests that the applied holding potential falls over a total distance of 10.4 A. In addition, at high positive holding potentials there is evidence for permeation of the trimethylammonium ions and a valency specific relief of block.
将纯化的绵羊心脏钙释放通道整合到平面磷脂双分子层中后，我们在电压钳制条件下研究了一系列单价（CH3-(CH2)n-1-N+(CH3)3）和二价（(CH3)3N(+)-(CH2)n-N+(CH3)3）三甲铵衍生物的阻断作用。所有测试的化合物都从通道的胞质面产生电压依赖性阻断。对于二价（Qn）衍生物，阻断的有效价随着链长的增加而降低，当链长n≥7时达到平台期。单价（Un）衍生物未观察到有效价下降。对这一现象的一种合理的解释表明，在所测量的90%的电压降中，链中添加一个CH2后长度的增加跨越了电场的12.7%。将此距离外推以包括其余10%表明，施加的保持电位在总距离10.4 Å上下降。此外，在高正保持电位下，有证据表明三甲铵离子发生渗透以及阻断的价态特异性缓解。
