Inhibition of cardiac Na+ currents by isoproterenol.
Inhibition of cardiac Na+ currents by isoproterenol.
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DOI：
10.1152/ajpheart.1990.258.4.h977
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发表时间：
1990-04
期刊：
影响因子：
--
通讯作者：
B. Schubert;A. VanDongen;G. Kirsch;A. Brown
中科院分区：
文献类型：
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作者：
B. Schubert;A. VanDongen;G. Kirsch;A. Brown
本文用膜片钳技术研究了β-肾上腺素能激动剂异丙肾上腺素（ISO）对新生大鼠单个心室肌细胞电压依赖性钠电流（INa）的调节机制。ISO可逆地抑制INa，使得该效应容易与全细胞膜片钳实验期间通常发生的门控偏移引起的INa的单调降低区分开（E.芬威克，A. Marty和E. Neher，J. Physiol. Lond. 331：599-635，1982;和J. M.费尔南德斯，A. P. Fox和S. Krasne，J. Physiol. Lond. 356：565-585，1984）。抑制是双相的，有快和慢的组件，是电压依赖性的，在去极化电位更明显。在全细胞实验中，膜渗透性腺苷3 '，5'-环一磷酸（cAMP）同源物8-溴-cAMP减少INa。在移液器中存在ISO的无细胞由内而外贴片中，应用于膜贴片内侧的鸟苷5 '-三磷酸（GTP）抑制单个Na+通道活性。这种抑制作用可被超极化预脉冲部分逆转。不可水解的GTP类似物鸟苷-5 '-O-（3-硫代三磷酸）以Mg 2（+）依赖性方式大大降低了单个Na+通道电流的可能性。我们建议，ISO抑制心脏Na+通道通过鸟嘌呤核苷酸结合，信号转导G蛋白，通过直接（膜界定）和间接（细胞质）途径的行为。
The mechanism by which the beta-adrenergic agonist isoproterenol (ISO) modulates voltage-dependent cardiac Na+ currents (INa) was studied in single ventricular myocytes of neonatal rat using the gigaseal patch-clamp technique. ISO inhibited INa reversibly, making the effect readily distinguishable from the monotonic decrease of INa caused by the shift in gating that customarily occurs during whole cell patch-clamp experiments (E. Fenwick, A. Marty, and E. Neher, J. Physiol. Lond. 331: 599-635, 1982; and J. M. Fernandez, A. P. Fox, and S. Krasne, J. Physiol. Lond. 356: 565-585, 1984). The inhibition was biphasic, having fast and slow components, and was voltage-dependent, being more pronounced at depolarized potentials. In whole cell experiments the membrane-permeable adenosine 3',5'-cyclic monophosphate (cAMP) congener 8-bromo-cAMP reduced INa. In cell-free inside-out patches with ISO present in the pipette, guanosine 5'-triphosphate (GTP) applied to the inner side of the membrane patch inhibited single Na+ channel activity. This inhibition could be partly reversed by hyperpolarizing prepulses. The nonhydrolyzable GTP analogue guanosine-5'-O-(3-thiotriphosphate) greatly reduced the probability of single Na+ channel currents in a Mg2(+)-dependent manner. We propose that ISO inhibits cardiac Na+ channels via the guanine nucleotide binding, signal-transducing G protein that acts through both direct (membrane delimited) and indirect (cytoplasmic) pathways.