PH REGULATION IN VENTRICULAR CELLS

哺乳动物心肌的电活动和机械活动是 受到当地酸碱度变化的显著影响。因此，细胞内 心室肌的酸碱控制是至关重要的 维持正常的心脏功能。哺乳动物的离子基础 在PHi大于7.1的情况下，心室的PHi控制是未知的，并且是 这项提案的重点。在许多类型的细胞中，包括心脏浦肯野 细胞，phi从细胞内碱中毒中恢复是通过 与Na无关的Cl-H C03交换。我们的初步发现提供了 强有力的证据表明，这种交换在哺乳动物的心脏中是可操作的 细胞。 不依赖于钠的氯-HCO3交换的定量性质将是 在本提案中，根据其对pH的敏感性、氯化物 依赖性，对细胞内碱中毒恢复的贡献， 对抑制剂的敏感性，以及在相反模式下的操作(Clout： HCO3英寸)所有实验都将在单个脑室上进行 成年豚鼠心肌细胞的快速溶液切换器和 细胞内H(snarf-1)和H(snarf-1)荧光指示剂 CL-(MQAE)。这一结果应该会为我们提供关于 心室phi调控的离子基础。

The electrical and mechanical activity of mammalian ventricular muscle is significantly affected by alterations in local pH. Hence, intracellular acidbase control in ventricular muscle is critically important for maintenance of normal heart function. The ionic basis of mammalian ventricular pHi control at pHi greater than 7.1 is unknown and is the focus of this proposal. In many cell types, including cardiac Purkinje cells, pHi recovery from intracellular alkalosis is mediated by Na-independent Cl-H C03 exchange. Our preliminary findings provide strong evidence the exchange is operational in mammalian ventricular cells . The quantitative properties of Na-independent Cl-HCO3 exchange will be examined in this proposal in terms of its pH sensitivity, chloride dependence, contribution to recovery from intracellular alkalosis, sensitivity to inhibitors, and operation in the reverse mode (Cl out: HCO3 in). All experiments will be performed on single ventricular myocytes from adult guinea pigs using a rapid solution switcher and fluorescent indicators for intracellular measurement of H + (SNARF-1) and Cl- (MQAE). The results should provide useful new insight concerning the ionic basis of ventricular pHi control.