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PH REGULATION IN VENTRICULAR CELLS

心室细胞的 PH 调节

基本信息

批准号：
2220724
负责人：
KENNETH W SPITZER
金额：
$ 9.63万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-07-01 至 1995-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2220724
关键词：
acidity /alkalinity catecholamines cell type fluorescent dye /probe guinea pigs heart contraction heart disorder heart ventricle hormone regulation /control mechanism insulin membrane potentials microelectrodes sarcolemma single cell analysis

项目摘要

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.

哺乳动物心室肌的电活动和机械活动是受局部 pH 值变化的影响显着。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，并且是本提案的重点。在许多细胞类型中，包括心脏浦肯野细胞细胞中，细胞内碱中毒的 pHi 恢复是由以下因素介导的不依赖Na的Cl-H CO 3 交换。我们的初步调查结果表明强有力的证据表明这种交换在哺乳动物心室中起作用细胞。不依赖 Na 的 Cl-HCO3 交换的定量特性为本提案检查了其 pH 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反向模式下的操作（Cl 输出： HCO3 中）。所有实验将在单心室上进行使用快速溶液切换器从成年豚鼠获得的肌细胞和用于细胞内测量 H + 的荧光指示剂 (SNARF-1) 和 Cl-(MQAE)。结果应该提供有关以下方面的有用的新见解：心室 pHi 控制的离子基础。