POTENTIAL-DEPENDENT AND TIME-DEPENDENT BLOCKADE OF INWARD RECTIFICATION IN FROG SKELETAL-MUSCLE FIBERS BY BARIUM AND STRONTIUM IONS

POTENTIAL-DEPENDENT AND TIME-DEPENDENT BLOCKADE OF INWARD RECTIFICATION IN FROG SKELETAL-MUSCLE FIBERS BY BARIUM AND STRONTIUM IONS
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DOI:
10.1113/jphysiol.1978.sp012379
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发表时间:
1978-01-01
影响因子:
5.5
通讯作者:
STANFIELD, PR
STANFIELD, PR
中科院分区:
医学1区
文献类型:
--
作者:
STANDEN, NB;STANFIELD, PR

文献摘要

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采用三电极电压钳法研究Ba2+和Sr2+对静息蛙缝匠肌纤维内向整流K电导的影响。当 Ba2+ (0.01-5 mM) 添加到对照 (115 mM-K+) 溶液中时,随着 Ba2+ 阻断的发展,超极化电压阶跃期间记录的内向电流随时间呈指数关闭。外向电流没有表现出时间依赖性。 Ba2+ 降低了超极化时记录的电流的瞬时值和稳态值。这种封锁是依赖于电位的,稳态电流随着超极化的增加而逐渐减少。 Ba2+ 阻断瞬时电流的浓度效应关系可以假设 Ba2+ 与受体以 1:1 的比例结合,且阻断与 Ba2+ 填充的受体的数量成正比。保持电位 (-5 mV) 下的表观解离常数为 0.65 mM。通过超极化,浓度效应关系沿着浓度轴移动到较低浓度。表观解离常数降低了 e 倍,电位变化为 16.8 mV。增加[Ba]o 增加了在给定电势下阻断的发生速率。封锁的发生率具有很高的温度依赖性(Q10 = 3.15.+-.0.08)。当 [K]o 加倍至 230 mM 时,在 [K]i 也加倍的条件下,[Ba]o 必须提高约 4 倍才能产生相同程度和速率的阻断。类似地,当 [K]o 减少时,对于给定的 [Ba]o,阻断的程度和发生率会增加。通过从沐浴溶液中去除 Ba2+ 可以很容易地消除这种封锁。超极化产生的封锁在恢复到保持潜力时也会以指数方式消除。存在于保持电势的封锁可以通过去极化预脉冲来去除。 Sr 会产生与 Ba2+ 类似的电位依赖性阻断作用,但效果要低 400 倍左右。结果与模型相拟合,假设渗透机制是具有结合 1 Ba2+ 或 2 K+ 的位点的水孔。该位点必须对 Ba2+ 具有高亲和力,对 K+ 具有低亲和力。
A 3-electrode voltage clamp method was used to investigate effects of Ba2+ and Sr2+ on the inwardly rectifying K conductance of resting frog sartorius muscle fibers. When Ba2+ (0.01-5 mM) was added to the control (115 mM-K+) solution, inward currents recorded during hyperpolarizing voltage steps turned off exponentially with time as the blockade by Ba2+ developed. Outward currents showed no time-dependence. Ba2+ reduced the instantaneous and steady-state values of currents recorded on hyperpolarization. The blockade was potential-dependent, steady-state currents being increasingly reduced with increasing hyperpolarization. The concentration-effect relation for blockade of instantaneous currents by Ba2+ could be fitted assuming 1:1 binding of Ba2+ to a receptor, with the block being proportional to the number of Ba2+-filled receptors. The apparent dissociation constant at the holding potential (-5 mV) was 0.65 mM. Concentration-effect relations were shifted along the concentration axis to lower concentrations by hyperpolarization. The apparent dissociation constant was reduced e-fold for a 16.8 mV change in potential. Increasing the [Ba]o increased the rate of onset of the blockade at a given potential. The rate of onset of the blockade had a high temperature dependence (Q10 = 3.15 .+-. 0.08). When [K]o was doubled to 230 mM, under conditions where [K]i was also doubled, [Ba]o had to be raised approximately 4-fold to produce the same degree and rate of onset of blockade. Similarly, when [K]o was decreased, degree and rate of onset of blockade were increased for a given [Ba]o. The blockade could be readily removed by removal of Ba2+ from the bathing solution. The blockade which develops on hyperpolarization also is removed exponentially on return to the holding potential. The blockade which exists at the holding potential may be removed by a depolarizing prepulse. Sr causes a similar potential-dependent blockade to that by Ba2+, but is around 400 times less effective. The results were fitted with a model assuming that the permeability mechanism is an aqueous pore with a site which binds 1 Ba2+ or 2 K+. The site must have a high affinity for Ba2+ and a low affinity for K+.