Elliott J R, Haydon D A, Hendry B M
J Physiol. 1984 May;350:429-45. doi: 10.1113/jphysiol.1984.sp015210.
The effects of octyltrimethylammonium ions (OTMA+), octyl sulphate ions (OS-) and octanoic acid (OA) on the sodium current of the voltage-clamped squid giant axon have been investigated using intracellular and extracellular application of the test substances. OTMA+ applied externally at concentrations of 0.8-5.0 mM produces a small reversible increase in the peak inward sodium current in both intact and CsF-perfused axons. Intracellular application of OTMA+ at 0.8 mM to CsF-perfused axons causes a reversible 50% suppression of peak inward sodium current. The inhibition of peak inward current by internal OTMA+ arises largely from a shift of the steady-state activation parameter (m infinity) in the depolarizing direction along the voltage axis. There is little use dependence of the current suppression by OTMA+ OA applied either internally or externally is more effective at suppressing peak inward sodium current at pH 6.0 than at pH 7.4. At pH 6.0 external application of 5 mM-OA to perfused axons causes approximately 60% suppression. This is associated with a depolarizing shift of m infinity of about 13 mV and a hyperpolarizing shift of the steady-state inactivation (h infinity) curve of about 4 mV. The effects of internal and external OA are broadly similar except that the h infinity shift is not seen with internal application. OS- at concentrations above 2.0 mM produces complete irreversible loss of sodium current. At 2.0 mM, OS- produces 10% current suppression and a small depolarizing shift of the m infinity curve. Internal and external applications of OS- differ little except that external OS- causes a 25% increase in the time constant of activation (tau m). The possible origins of these effects are discussed. It is proposed that the shift of m infinity caused by internal OTMA+ is due to a diminution of the lipid dipole potential at the internal surface of the membrane caused by OTMA+ adsorption. This effect could also account for the m infinity shift caused by OA. The results showing that OA produces shifts of opposite sign in the voltage dependence of m infinity and h infinity are discussed with respect to their implications for models of sodium channel gating.
利用测试物质的细胞内和细胞外应用，研究了辛基三甲基铵离子（OTMA⁺）、辛基硫酸根离子（OS⁻）和辛酸（OA）对电压钳制的枪乌贼巨大轴突钠电流的影响。外部施加浓度为0.8 - 5.0 mM的OTMA⁺会使完整和CsF灌注轴突的内向钠电流峰值产生小幅可逆增加。向CsF灌注轴突细胞内施加0.8 mM的OTMA⁺会使内向钠电流峰值产生50%的可逆抑制。内部OTMA⁺对内向电流峰值的抑制主要源于稳态激活参数（m无穷大）沿电压轴在去极化方向上的偏移。OTMA⁺对电流的抑制几乎没有使用依赖性。内部或外部施加的OA在pH 6.0时比在pH 7.4时更有效地抑制内向钠电流峰值。在pH 6.0时，向灌注轴突外部施加5 mM - OA会导致约60%的抑制。这与m无穷大约13 mV的去极化偏移和稳态失活（h无穷大）曲线约4 mV的超极化偏移有关。内部和外部OA的作用大致相似，只是内部施加时未观察到h无穷大的偏移。浓度高于2.0 mM的OS⁻会导致钠电流完全不可逆丧失。在2.0 mM时，OS⁻会产生10%的电流抑制和m无穷大曲线的小幅去极化偏移。内部和外部施加OS⁻的差异不大，只是外部OS⁻会使激活时间常数（τm）增加25%。讨论了这些效应可能的起源。有人提出，内部OTMA⁺引起的m无穷大偏移是由于OTMA⁺吸附导致膜内表面脂质偶极电位降低。这种效应也可以解释OA引起的m无穷大偏移。针对OA在m无穷大和h无穷大电压依赖性上产生相反符号偏移的结果，讨论了它们对钠通道门控模型的影响。
