Extracellular divalent cations block a cation non-selective conductance unrelated to calcium channels in rat cardiac muscle

Extracellular divalent cations block a cation non-selective conductance unrelated to calcium channels in rat cardiac muscle
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DOI:
10.1111/j.1469-7793.1997.235bk.x
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发表时间:
1997-07-15
影响因子:
5.5
通讯作者:
Flameng, W
Flameng, W
中科院分区:
医学1区
文献类型:
--
作者:
Mubagwa, K;Stengl, M;Flameng, W

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1.研究了去细胞外二价阳离子对大鼠心肌细胞静息电位(V-REST)和背景电导的影响。在乳头肌用3M KCl微电极或在心室肌细胞用贴片电极测量V-REST。采用阶跃或斜波电压指令测量心肌细胞的全细胞膜电流。在肌肉和单个细胞中,Ca-0(2+)和Mg-0(2+)的减少或去除都会引起硝苯地平抵抗的去极化,重新接纳Ca-0(2+)或Mg-0(2+)时,这种作用被逆转(肌肉中0.8 mM的Ca-0(2+)或3 mM的Mg-0(2+)的半最大效应)。在单个心肌细胞中,去除Ca-0(2+)和Mg-0(2+)对非断裂细胞附着记录的封闭电阻没有影响,但在全细胞记录中可逆地诱导出翻转电位(V-rev)为-8+/-3.4 mV(有内部Cs+;平均+/-S.E.M.,n=23)的电流。该电流对硝苯地平(3~100µm)或阿米洛利(1 Mm)不敏感。V-rev对氯离子平衡电势(E-Cl)的变化不敏感。Ca-0(2+)以浓度依赖的方式阻断无细胞外二价阳离子时的电流。在-80 mV时,亲和常数K-Ca为60µM,希尔系数为0.9。K-Ca在正电位下呈电压依赖性,而在负电位下不呈电压依赖性。Mg-0(2+)、Ni-0(2+)、Sr-0(2+)、Ba0(2+)、Cd-0(2+)和Gd-0(3+)对电流也有抑制作用。在0 mM Na+(145 mM NMDG(+))中,二价阳离子敏感电流的内向分量减少,V-rev向更负的电位移动。这些结果表明,在心室肌细胞中存在一种新的电导通路,该通路对单价阳离子具有通透性,对氯离子不具有通透性,但可被二价阳离子阻断。
1. The effect of removing extracellular divalent cations on resting potential (V-rest) and background conductance of rat cardiac muscle was studied. V-rest was measured with 3 M KCl-filled microelectrodes in papillary muscles, or with a patch electrode in ventricular myocytes. Whole-cell membrane currents were measured in myocytes using step or ramp voltage commands.2. In both muscles and single cells, decrease or removal of Ca-0(2+) and Mg-0(2+) caused a nifedipine-resistant depolarization, which was reversed upon readmission of Ca-0(2+) or Mg-0(2+) (half-maximal effect at 0.8 mM Ca-0(2+) or 3 mM Mg-0(2+) in muscles).3. In single myocytes, removal of Ca-0(2+) and Mg-0(2+) had no effect on the seal resistance in nonruptured cell-attached recordings, but reversibly induced a current with a reversal potential (V-rev) of -8+/-3.4 mV (with internal Cs+; mean+/-S.E.M., n=23) during whole-cell recordings. The current was insensitive to nifedipine (3-100 mu m) or amiloride (I mm). V-rev was insensitive to changes in the equilibrium potential for chloride ions (E-Cl).4. The current induced in the absence of extracellular divalent cations was blocked in a concentration-dependent manner by Ca-0(2+). (At -80 mV, the affinity constant K-Ca was 60 mu M with a Hill coefficient of 0.9.) K-Ca was voltage dependent at positive but not negative potentials. Mg-0(2+), Ni-0(2+), Sr-0(2+), Ba-0(2+), Cd-0(2+) and Gd-0(3+) also blocked the current.5. In 0 mM Na+ (145 mM NMDG(+)), the inward component of the divalent cation-sensitive current was decreased and V-rev shifted to more negative potentials.6. These results suggest that a novel conductance pathway, permeable to monovalent cations but not to Cl- and blocked by divalent cations, exists in ventricular myocytes.