Glucagon induces suppression of ATP-sensitive K+ channel activity through a Ca2+/calmodulin-dependent pathway in mouse pancreatic β-cells

被引:12
作者
He, LP [1 ]
Mears, D
Atwater, I
Kitasato, H
机构
[1] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA
[2] Shiga Univ Med Sci, Dept Physiol, Ohtsu, Shiga 52021, Japan
关键词
cAMP; calmodulin antagonist; caged Ca2+; islet of Langerhans; glycogenolysis;
D O I
10.1007/s002329900465
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glucagon is known to increase intracellular cAMP levels and enhance glucose-induced electrical activity and insulin secretion in pancreatic beta-cell perfused with Krebs-Ringer bicarbonate solution. The present experiments were aimed at evaluation of the hypothesis that changes in beta-cells ATP-sensitive K+ (K-(ATP)) channel activity are involved in the glucagon-induced enhancement of electrical activity. Channel activity was recorded using the cell-attached configuration of the patch-clamp technique. Addition of glucagon (2.9 x 10(-7) M) in the presence of 11.1 mM glucose caused closure of K-(ATP) channels followed by an increase in the frequency of biphasic current transients (action currents) due to action potential generation in the cell. Three calmodulin-antagonists (W-7, chlorpromazine, and trifluoperazine) restored with similar efficacy K-(ATP) channel activity in cells being exposed to glucagon. At 2.8 mM glucose, glucagon did not affect K-(ATP) channel activity until Ca2+ was released from Nitr-5 by flash photolysis, at which point channel activity was transiently suppressed. Similar effects were seen when db-cAMP was used instead of glucagon. These results support the view that glucagon and other cAMP-generating agonists enhance glucose-induced beta-cell electrical activity through a Ca2+/calmodulin dependent-closure of K-(ATP) channels.
引用
收藏
页码:237 / 244
页数:8
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