Fernández J M, Taylor R E, Bezanilla F
J Gen Physiol. 1983 Sep;82(3):331-46. doi: 10.1085/jgp.82.3.331.
Voltage-clamped squid giant axons, perfused internally and externally with solutions containing 10(-5) M dipicrylamine (DpA-), show very large polarization currents (greater than or equal to 1 mA/cm2) in response to voltage steps. The induced polarization currents are shown in the frequency domain as a very large voltage-and frequency-dependent capacitance that can be fit by single Debye-type relaxations. In the time domain, the decay phase of the induced currents can be fit by single exponentials. The induced polarization currents can also be observed in the presence of large sodium and potassium currents. The presence of the DpA- molecules does not affect the resting potential of the axons, but the action potentials appear graded, with a much-reduced rate of rise. The data in the time domain as well as the frequency domain can be explained by a single-barrier model where the DpA- molecules translocate for an equivalent fraction of the electric field of 0.63, and the forward and backward rate constants are equal at -15 mV. When the induced polarization currents described here are added to the total ionic current expression given by Hodgkin and Huxley (1952), numerical solutions of the membrane action potential reproduce qualitatively our experimental data. Numerical solutions of the propagated action potential predict that large changes in the speed of conduction are possible when polarization currents are induced in the axonal membrane. We speculate that either naturally occurring substances or drugs could alter the cable properties of cells in a similar manner.
电压钳制的枪乌贼巨大轴突,内外灌注含有10(-5)M二硝基苯胺(DpA-)的溶液,在电压阶跃时显示出非常大的极化电流(大于或等于1 mA/cm2)。诱导的极化电流在频域中表现为非常大的电压和频率依赖性电容,可以用单个德拜型弛豫来拟合。在时域中,诱导电流的衰减阶段可以用单个指数来拟合。在存在大的钠电流和钾电流的情况下也可以观察到诱导的极化电流。DpA-分子的存在不影响轴突的静息电位,但动作电位呈分级状,上升速率大大降低。时域和频域中的数据可以用单势垒模型来解释,其中DpA-分子在等效电场的0.63部分发生移位,正向和反向速率常数在-15 mV时相等。当这里描述的诱导极化电流添加到霍奇金和赫胥黎(1952)给出的总离子电流表达式中时,膜动作电位的数值解定性地再现了我们的实验数据。传播动作电位的数值解预测,当轴突膜中诱导极化电流时,传导速度可能会发生很大变化。我们推测,天然存在的物质或药物可能会以类似的方式改变细胞的电缆特性。