French R J, Shoukimas J J
Biophys J. 1981 May;34(2):271-91. doi: 10.1016/S0006-3495(81)84849-7.
We have studied the effects of the tetra-n-alkylammonium (TAA) ions, (CnH2n+1)4N+, n = 1-6, on the potassium conductance of voltage-clamped squid giant axons. Studies using tetrahexylammonium were not quantitatively analyzed as its effect was insufficiently reversible. Each in this series of symmetric ions of graded size blocks the potassium conductance when added to the internal perfusion fluid. There is a general trend for blocking potency to increase with increasing size. We attribute this to stronger interactions of the longer alkyl side chains with hydrophobic regions of the membrane near the channels. Steady-state block by the TAA ions, n = 2-5, showed identical voltage dependence, apparently sensing about 15% of the transmembrane voltage, and kinetics block onset were qualitatively similar. We conclude that the site of action for these ions is the same. Block by TMA is about twice as steeply dependent on voltage. In its action, TMA resembles the alkali cations (French et al., 1979, Biophys, J. 25(2, pt. 2):307a) more than the larger TAA ions. Our results suggest that access to the inner mouth of the K channel is even less restricted than has been previously thought. A calculation indicates that the lumen of the channel cannot be both wide enough to admit the TAA ions and long enough to account for the voltage dependence of block. We consider possible ways to resolve this paradox.
我们研究了四正烷基铵（TAA）离子（CnH2n+1）4N+，n = 1 - 6，对电压钳制的枪乌贼巨大轴突钾电导的影响。由于四己基铵的作用可逆性不足，因此未对使用它的研究进行定量分析。这一系列大小渐变的对称离子中的每一种，添加到内部灌流液中时都会阻断钾电导。一般趋势是，阻断效力随离子大小增加而增强。我们将此归因于较长的烷基侧链与通道附近膜的疏水区域之间更强的相互作用。n = 2 - 5的TAA离子的稳态阻断表现出相同的电压依赖性，显然能感知约15%的跨膜电压，并且阻断起始动力学在定性上相似。我们得出结论，这些离子的作用位点相同。TMA的阻断对电压的依赖性大约陡两倍。在其作用中，TMA比更大的TAA离子更类似于碱金属阳离子（French等人，1979年，《生物物理学杂志》25(2, 第2部分):307a）。我们的结果表明，钾通道内口的可及性比之前认为的还要低。一项计算表明，通道腔不可能既宽到足以容纳TAA离子，又长到足以解释阻断的电压依赖性。我们考虑了解决这一矛盾的可能方法。
