Kirsch G E, Yeh J Z, Farley J M, Narahashi T
J Gen Physiol. 1980 Sep;76(3):315-35. doi: 10.1085/jgp.76.3.315.
The effects of n-alkylguanidine derivatives on sodium channel conductance were measured in voltage clamped, internally perfused squid giant axons. After destruction of the sodium inactivation mechanism by internal pronase treatment, internal application of n-amylguanidine (0.5 mM) or n-octylguanidine (0.03 mM) caused a time-dependent block of sodium channels. No time-dependent block was observed with shorter chain derivatives. No change in the rising phase of sodium current was seen and the block of steady-state sodium current was independent of the membrane potential. In axons with intact sodium inactivation, an apparent facilitation of inactivation was observed after application of either n-amylguanidine or n-octylguanidine. These results can be explained by a model in which alkylguanidines enter and occlude open sodium channels from inside the membrane with voltage-independent rate constants. Alkylguanidine block bears a close resemblance to natural sodium inactivation. This might be explained by the fact that alkylguanidines are related to arginine, which has a guanidino group and is thought to be an essential amino acid in the molecular mechanism of sodium inactivation. A strong correlation between alkyl chain length and blocking potency was found, suggesting that a hydrophobic binding site exists near the inner mouth of the sodium channel.
在电压钳制、内部灌注的鱿鱼巨轴突中测量了正烷基胍衍生物对钠通道电导的影响。在用内部链霉蛋白酶处理破坏钠失活机制后，内向施加正戊基胍（0.5 mM）或正辛基胍（0.03 mM）会引起钠通道的时间依赖性阻断。对于较短链的衍生物，未观察到时间依赖性阻断。钠电流上升相未见变化，稳态钠电流的阻断与膜电位无关。在钠失活完整的轴突中，施加正戊基胍或正辛基胍后观察到明显的失活促进作用。这些结果可以用一个模型来解释，即烷基胍以与电压无关的速率常数从膜内部进入并堵塞开放的钠通道。烷基胍阻断与天然钠失活非常相似。这可能是因为烷基胍与精氨酸有关，精氨酸含有胍基，被认为是钠失活分子机制中的必需氨基酸。发现烷基链长度与阻断效力之间存在强相关性，表明在钠通道内口附近存在一个疏水结合位点。
