Kaibara M, Mitarai S, Yano K, Kameyama M
Third Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Circ Res. 1994 Dec;75(6):1121-5. doi: 10.1161/01.res.75.6.1121.
The present study investigated the possible involvement of a Na(+)-H+ antiporter in the regulation of L-type Ca2+ channels by angiotensin II (Ang II) in isolated rabbit ventricular cardiac myocytes by using both cell-attached and whole-cell patch-clamp current recording techniques. In cell-attached patch-clamp current recordings, an increase in the open-state probability of the Ca2+ channel (144.8 +/- 9.8% [mean +/- SEM], n = 11) was seen after exposure of the cells to Ang II (100 nmol/L). This effect was inhibited by pretreatment with losartan (10 mumol/L), a synthetic antagonist of the AT1 receptor. 5(N,N-Dimethyl)amiloride (100 mumol/L), an amiloride analogue, as well as Na(+)-deficient bath solution abolished Ang II-induced stimulation of the Ca2+ channel activities. In whole-cell patch-clamp current recordings, Ang II also increased the L-type Ca2+ current when a pipette solution of pH 7.1 containing 5 mmol/L HEPES (139 +/- 5%, n = 4) was used but did not significantly increase the current when a pipette solution of pH 7.5 containing 5 mmol/L HEPES or a pipette solution of pH 7.1 containing 30 mmol/L HEPES was used. These results suggest that Ang II-induced stimulation of the Ca2+ channels is mediated by a Na(+)-H+ antiporter and therefore provide a novel insight into signal transduction of Ang II receptor stimulation in cardiac myocytes.
本研究采用细胞贴附式和全细胞膜片钳电流记录技术，研究了在分离的兔心室肌细胞中，钠氢交换体（Na(+)-H+ antiporter）是否可能参与血管紧张素II（Ang II）对L型钙通道的调节。在细胞贴附式膜片钳电流记录中，将细胞暴露于Ang II（100 nmol/L）后，钙通道的开放概率增加（144.8 +/- 9.8% [平均值 +/- 标准误]，n = 11）。这种效应被氯沙坦（10 μmol/L）预处理所抑制，氯沙坦是AT1受体的合成拮抗剂。阿米洛利类似物5(N,N-二甲基)阿米洛利（100 μmol/L）以及无钠浴液消除了Ang II诱导的钙通道活性刺激。在全细胞膜片钳电流记录中，当使用含有5 mmol/L HEPES（pH 7.1）的移液管溶液时（139 +/- 5%，n = 4），Ang II也增加了L型钙电流，但当使用含有5 mmol/L HEPES（pH 7.5）的移液管溶液或含有30 mmol/L HEPES（pH 7.1）的移液管溶液时，电流没有显著增加。这些结果表明，Ang II诱导的钙通道刺激是由钠氢交换体介导的，因此为心肌细胞中Ang II受体刺激的信号转导提供了新的见解。
