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神经肽Y对心室肌细胞离子通道的影响

赵画晨, 刘忠保, 封启龙, 崔香丽, 张春敏, 吴博威

山西医科大学生理学教研室.山西,太原 030001

摘要

采用全细胞膜片钳技术观察神经肽Y(neuropeptide Y,NPY)对心室肌细胞离子通道的影响。结果如下：(1)NPY浓度在1.0---100nmol/L范围内剂量依赖性抑制大鼠心室肌细胞I_(Ca-L),IC_(50)值为1.86nmol/L。NPY对I_(Ca-L)的I--V曲线的最大峰值电位、激活和失活电位均无显著影响。NPY对去甲肾上腺素(norepinephrine,NE)增加的I_(Ca-L)有显著抑制作用。(2)NPY对人鼠心室肌细胞I_(Na/Ca)有显著抑制作用。10nmol/L NPY使前向I_(Na/Ca)由(0.27±0.11)pA/pF减小为(0.06±0.01)pA/pF；反向I_(Na/Ca)由(0.45±0.12)pA/pF降为(0.27±0.09)pA/pF({sl P}＜0.05,n=4)。(3)NPY对大鼠心室肌细胞I_(to)有显著增强作用。10 nmol/L NPY使I_(to)由(12.5±0.70)pA/pF增加至(14.7±0.59)pA/pF({sl P}＜0.05,n=4)。(4)10nmol/L NPY对大鼠心室肌细胞I_(Na)没有显著影响。(5)10nmol/L NPY对豚鼠心室肌细胞I_(K)无明显影响。研究结果证实，NPY抑制大鼠心室肌细胞I_(Ca-L)和I_(Na/Ca)，增强I_(to)，对I_(Na)和豚鼠心室肌细胞I_(K)没有显著作用，表明NPY对上述主要离子通道的效应与NE的效应相拮抗。

关键词： 神经肽Y; 膜片钳技术; 心肌; 离子通道

Effects of neuropeptide Y on ion channels in ventricular myocytes

Zhao Huachen, Liu Zhongbao, Feng Qilong, Cui Xiangli, Zhang Chunmin, Wu Bowei

Department of physiology, Shanxi Medical University.Taiyuan 030001,Shanxi

Abstract

Neuropeptide Y (NPY) co-exists with norepinephrine (NE) in sympathetic terminals, and is the most abundant neuropeptide in myocardium. Many studies have focused on the effects of NE on ion channels in cardiac myocytes and its physiological significance have been elucidated relatively profoundly. There have been few investigations, however, on the physiological significance of NPY in myocardium. The effects of NPY on L-type Ca~(2+) channel currents (I_(Ca-L)) were evaluated in some studies and different results were presented, which might be attributed to the different species of animal tested and different methods used. It is necessary, therefore, to study the effects of NPY on ion channels in cardiac myocytes systematically and further to discuss the biological significance of their coexistence with NE in sympathetic terminals. The single ventricular myocytes from adult rat or guinea pig (only for measuring I_(K)) were prepared using enzymatic dispersion. I_(Ca-L), I_(to), I_(Na/Ca), I_(Na) and I_(K) in the cellular membrane were observed using whole cell voltage-clamp recording. In the present study, NPY from 1.0 nmol/L to 100 nmol/L dose-dependently inhibited I_(Ca-L) (P<0.01, n=5). The maximal rate of inhibition in this study reached 39% and IC_(50) was 1.86 nmol/L. NPY had no effect on the voltage-dependence of calcium current amplitude and on the voltage-dependence of the steady-state gating variables. I_(Ca-L) was activated at -30 mV, reaching maximum at 0 mV. When both NE and NPY were applied with a concentration ratio of 500:1, 10 nmol/L NPY inhibited I_(Ca-L) that had been increased by 5 #mu#mol/L NE, which was consistent with the effect of NPY only on I_(Ca-L). NPY also inhibited I_(Na/Ca). At a concentration of 10 nmol/L, NPY inhibited inward and outward I_(Na/Ca) from (0.27±0.11) pA/pF and (0.45±0.12) pA/pF to (0.06±0.01) pA/pF and (0.27±0.09) pA/pF, respectively (P<0.05，n＝4). NPY at 10 nmol/L increased Ito from (12.5±0.70) pA/pF to (14.7±0.59) pA/pF (P<0.05，n＝4). NPY at 10 nmol/L did not affect I_(Na) in rat myocytes and I_(K) in guinea pig myocytes. The effects of NPY on I_(Ca-L), I_(Na/Ca) and I_(to) all increased the speed of action potential depolarization and reduced action potential duration, which contributed to the reduction of contraction. These results indicate that the effects of NPY are opposite to the effects of NE on ion channels of cardiac myocytes.

Key words: Neuropeptide Y;Patch-clamp techniques;Myocardium;ion channels

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引用本文：

赵画晨, 刘忠保, 封启龙, 崔香丽, 张春敏, 吴博威. 神经肽Y对心室肌细胞离子通道的影响[J]. 生理学报 2006; 58 (3): .

Zhao Huachen, Liu Zhongbao, Feng Qilong, Cui Xiangli, Zhang Chunmin, Wu Bowei. Effects of neuropeptide Y on ion channels in ventricular myocytes. Acta Physiol Sin 2006; 58 (3): (in Chinese with English abstract).