PH REGULATION IN VENTRICULAR CELLS

哺乳动物心室肌的电和机械活动是 受局部pH值变化的显著影响。因此，细胞内 心室肌的酸碱控制对于 维持正常的心脏功能。 哺乳动物的离子基础 pHi大于7.1时的心室pHi控制未知， 这一提案的重点。 在许多细胞类型中，包括心脏浦肯野细胞 细胞，细胞内pH恢复是介导的 Na非依赖性Cl-H CO 3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心室 细胞 非Na依赖性Cl-HCO 3交换的定量性质将是 在本提案中，根据其pH敏感性，氯化物 依赖性，有助于从细胞内水肿中恢复， 对抑制剂的敏感性，以及反向模式下的操作（Cl out： HCO3 in）。 所有实验将在单心室 使用快速溶液转换器从成年豚鼠的肌细胞中， 用于细胞内测量H +的荧光指示剂（SNARF-1）， Cl-（MQAE）。 这些结果应该提供有用的新见解， 心室pHi控制的离子基础。

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.