Pharmacological approach toward the pacemaker mechanism of porcine sinoatrial node cells

点击翻译按钮获取中文摘要

This project was carried out to investigate the mechanisms underlying the automaticity of porcine sinoatrial node cells, and the following results were obtained.1. The isolated cells exhibited spontaneous action potentials at a rate of approximately 80 minィイD1-1ィエD1. This value is similar to the heart rate of pigs and slower than that of rabbit sinoatrial node cell (approximately 200 minィイD1-1ィエD1), indicating that the heart rate is determined by intrinsic properties of sinoatrial node cells of various mammalian species.2. In porcine sinoatrial node cells the delayed rectifier KィイD1+ィエD1 current (IィイD2KィエD2) is largely derived from the slowly activating IィイD2KィエD2 (IィイD2KsィエD2). The result suggest that IィイD2KsィエD2 may, in part, account for the relatively slower heart rate of pigs than rabbit in which the rapidly activating IィイD2KィエD2 (IィイD2KrィエD2) is predominant component of IK.3. The hyperpolarization-activated cation current (IィイD2hィエD2) activates at membrane potentials more negative … More than -70 mV. The kinetics and ionic selectivity were essentially similar to IィイD2hィエD2 of rabbit sinoatrial node cells.4. Chromanol derivative 293B blocks IィイD2KsィエD2 selectively. In guinea-pig ventricular cells, block by chromanol 293B of IィイD2KsィエD2 occurred in a time-dependent manner. We conclude that chromanol 293B is an open channel blocker for IィイD2KsィエD2 with a relatively slower blocking rate constant than those reported so far for time- and voltage-dependent blockade of ionic channels.It has been reported that various ionic currents such as IィイD2KィエD2, IィイD2hィエD2, L- and T-type CaィイD12+ィエD1 currents, NaィイD1+ィエD1/KィイD1+ィエD1 pump current, background cation current, muscarinic KィイD1+ィエD1 current and dyhydropyridine-sensitive NaィイD1+ィエD1 current, contribute to the automaticity of sinoatrial node cells. Although we could successfully quantify the properties of IK and Ih in porcine sinoatirial node cells in this project, the characteristics of other ionic currents still remain to be evaluated. Less