ATP-SENSITIVE K+ CURRENTS IN CEREBRAL ARTERIAL SMOOTH-MUSCLE - PHARMACOLOGICAL AND HORMONAL MODULATION

被引:75
作者
KLEPPISCH, T [1 ]
NELSON, MT [1 ]
机构
[1] UNIV VERMONT, VERMONT CTR VASC RES, DEPT PHARMACOL, SMOOTH MUSCLE ION CHANNEL GRP, COLCHESTER, VT 05446 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1995年 / 269卷 / 05期
关键词
GLIBENCLAMIDE; PINACIDIL; LEVCROMAKALIM; CEREBRAL ISCHEMIA; ADENOSINE; CALCITONIN GENE-RELATED PEPTIDE; TETRAETHYLAMMONIUM; 4-AMINOPYRIDINE; IBERIOTOXIN; VASCULAR TONE;
D O I
10.1152/ajpheart.1995.269.5.H1634
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Calcitonin gene-related peptide (CGRP), hypoxia, and synthetic activators of ATP-sensitive potassium (K-ATP) channels (e.g., pinacidil and levcromakalim) cause dilation of cerebral arteries that are attenuated by the K-ATP channel inhibitor glibenclamide. We have identified and characterized K-ATP currents in smooth muscle cells isolated from rabbit cerebral arteries, using the whole cell configuration of the patch-clamp technique. Pinacidil (10 mu M) and levcromakalim (10 mu M) increased glibenclamide-sensitive currents about sixfold in cells dialyzed with 0.1 mM ATP. Glibenclamide-sensitive currents in the presence of pinacidil were potassium selective, voltage independent, and reduced about threefold by elevating intracellular ATP from 0.1 to 3.0 mM. External tetraethylammonium and 4-aminopyridine at millimolar concentrations reduced pinacidil-induced currents, whereas iberiotoxin, a blocker of calcium-activated potassium channels, had no effect. The vasoconstrictors serotonin and histamine also inhibited pinacidil-induced currents. The vasodilators CGRP and adenosine, in contrast, increased glibenclamide-sensitive potassium currents. We conclude that cerebral artery smooth muscle cells have K-ATP channels that are regulated by endogenous vasoconstrictors and vasodilators. We propose that these channels are involved in the dilation of cerebral arteries to CGRP and synthetic vasodilators.
引用
收藏
页码:H1634 / H1640
页数:7
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