Rozanski G J, Witt R C
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha 68198-4575, USA.
J Mol Cell Cardiol. 1995 Sep;27(9):1781-8. doi: 10.1016/0022-2828(95)90001-2.
The beta-adrenergic control of the L-type Ca2+ current (ICa) was examined as a function of extracellular pH (pHo) in guinea-pig ventricular myocytes using the whole-cell voltage-clamp technique. ICa was elicited in Cs(+)-loaded myocytes by depolarizing pulses from a holding potential of -40 mV. The maximum ICa density in response to 0.01 or 1 microM isoproterenol was significantly less in myocytes pretreated with acidic external solution (pHo 6.6 or 5.8) compared with cells studied at control pHo 7.4. This acidosis-induced decrease in beta-responsiveness was also accompanied by a similar reduction in basal current density. Myocytes studied under alkaline conditions (pHo 8.2) also had reduced beta-responsiveness although basal ICa density tended to be greater than control. In addition to the diminished effects of isoproterenol, acidic myocytes had smaller responses to extracellular forskolin and internally applied adenosine 3',5'-cyclic monophosphate, compared with control. The blunted responses to these latter stimuli were similar in magnitude to that observed with 1 microM isoproterenol. These findings suggest that protons interfere with the beta-adrenergic control of ICa primarily by a direct inhibition of the Ca2+ channel which independently masks the effects of the adenylyl cyclase cascade.
运用全细胞电压钳技术，在豚鼠心室肌细胞中研究了L型钙电流（ICa）的β-肾上腺素能调控与细胞外pH（pHo）的关系。通过从-40 mV的 holding 电位进行去极化脉冲，在Cs(+)负载的肌细胞中诱发ICa。与在对照pHo 7.4下研究的细胞相比，用酸性外部溶液（pHo 6.6或5.8）预处理的肌细胞中，对0.01或1 microM异丙肾上腺素的最大ICa密度显著降低。这种酸中毒诱导的β反应性降低还伴随着基础电流密度的类似降低。在碱性条件（pHo 8.2）下研究的肌细胞也有β反应性降低，尽管基础ICa密度往往大于对照。除了异丙肾上腺素的作用减弱外，与对照相比，酸性肌细胞对细胞外福斯高林和内部施加的3',5'-环磷酸腺苷的反应较小。对这些后一种刺激的钝化反应在幅度上与用1 microM异丙肾上腺素观察到的相似。这些发现表明，质子主要通过直接抑制钙通道来干扰ICa的β-肾上腺素能调控，而钙通道独立地掩盖了腺苷酸环化酶级联反应的作用。
