MinK-Related Peptide 1 Associates With Kv4.2 and Modulates Its Gating FunctionPotential Role as &bgr; Subunit of Cardiac Transient Outward Channel?
作者:
Mei Zhang,
Min Jiang,
Gea-Ny Tseng,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2001)
卷期:
Volume 88,
issue 10
页码: 1012-1019
ISSN:0009-7330
年代: 2001
出版商: OVID
关键词: Kv channel &bgr; subunits;long QT;rapid component of delayed rectifier channels;transient outward channels;Xenopusoocytes
数据来源: OVID
摘要:
Abstract—Inherited mutations and a polymorphism in minK-related peptide 1 (MiRP1) have been linked to congenital or acquired long-QT syndrome, pointing to the importance of MiRP1 in maintaining the cardiac electrical stability. We tested whether MiRP1 could affect the function of Kv4.x (x=2 and 3), the major pore-forming (&agr;) subunits of transient outward (Ito) channels in the heart. We used theXenopusoocyte expression system to examine the effects of MiRP1 on Kv4.x channel gating kinetics and current amplitude and correlated these effects with MiRP1 expression level. MiRP1 slowed the rates of Kv4.2 activation and inactivation and shifted the voltage dependence of channel gating in the positive direction. These effects had a similar “dose” dependence: they plateaued at a cRNA ratio (MiRP1:Kv4.2) of 13:1, with half-maximum effects at estimated cRNA ratios of 2 to 4. On the other hand, MiRP1 had no significant effects on Kv4.2 current amplitude in the same range of expression level. When expressed at a comparable low level, MiRP1 had similar (although smaller) effects on Kv4.3 but could not modulate Kv1.4 (another &agr; subunit ofItochannels in the heart). Kv4.2 could be coimmunoprecipitated with epitope-tagged MiRP1, indicating that the 2 could form a stable complex. Our data suggest that MiRP1 may serve as a regulatory (&bgr;) subunit ofItochannels in the heart. This is supported by the observation that MiRP1 induced an “overshoot” of Kv4.2 current amplitude during channel recovery from inactivation, similar to the overshoot ofItodescribed for human epicardial myocytes.
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