PHOSPHORYLATION BY PROTEIN-KINASE-A ENHANCES DELAYED RECTIFIER K+ CURRENT IN RABBIT VASCULAR SMOOTH-MUSCLE CELLS

被引:113
作者
AIELLO, EA [1 ]
WALSH, MP [1 ]
COLE, WC [1 ]
机构
[1] UNIV CALGARY, FAC MED, DEPT PHARMACOL & THERAPEUT, SMOOTH MUSCLE RES GRP, CALGARY, AB T2N 4N1, CANADA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1995年 / 268卷 / 02期
关键词
ION CHANNELS; BETA-ADRENOCEPTORS; ISOPROTERENOL; FORSKOLIN; 4-AMINOPYRIDINE;
D O I
10.1152/ajpheart.1995.268.2.H926
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The effect of adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) activity on 4-aminopyridine (4-AP)-sensitive delayed rectifier current (I-dK) in isolated rabbit portal vein smooth muscle cells was studied via whole cell voltage clamp (20-22 degrees C). A threefold increase in 4-AP-sensitive (5 mM) I-dK was recorded after gaining cell access during dialysis with 5 mM intracellular ATP and internal Ca2+ buffered to a low level with 5 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Dialysis with the nonhydrolyzable ATP analogue 5'-adenylylimidodiphosphate (5 mM) or the specific peptide inhibitor of PKA (PKI; 10 mu M) reduced current runup by 50 and 70%, respectively. Delayed dialysis with PKI reversed runup and inhibited I-dK to below initial levels. Forskolin (1 mu M) caused a reversible increase in I-dK, which was inhibited by 4-AP (5 mM). Isoproterenol (1 mu M) reversibly enhanced I-dK; the increase was sensitive to propranolol (2 mu M) and 4-AP (5 mM) and was prevented by dialysis with PKI (10 mu M) I-dK was enhanced over the entire voltage range of activation and associated with a negative shift in reversal potential of net whole cell current, consistent with hyperpolarization of resting membrane potential. The data provide the first evidence for a signal transduction mechanism involving beta-adrenoceptors, adenylate cyclase, and a phosphotransferase reaction mediated by PKA for the regulation of delayed rectifier K+ channels in vascular smooth muscle.
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页码:H926 / H934
页数:9
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