Defective “pacemaker” current ( I h ) in a zebrafish mutant with a slow heart rate

起搏器电位 斑马鱼 心跳 去极化 心室动作电位 生物 达尼奥 心脏起搏器 细胞生物学 内科学 突变体 河豚毒素 胚胎心脏 心肌细胞 生物物理学 电生理学 神经科学 遗传学 胚胎干细胞 医学 基因 复极 计算机科学 计算机安全
作者
Keith Baker,Kerri S. Warren,Gary Yellen,Mark C. Fishman
出处
期刊:Proceedings of the National Academy of Sciences of the United States of America [Proceedings of the National Academy of Sciences]
卷期号:94 (9): 4554-4559 被引量:206
标识
DOI:10.1073/pnas.94.9.4554
摘要

At a cellular level, cardiac pacemaking, which sets the rate and rhythm of the heartbeat, is produced by the slow membrane depolarization that occurs between action potentials. Several ionic currents could account for this pacemaker potential, but their relative prominence is controversial, and it is not known which ones actually play a pacemaking role in vivo . To correlate currents in individual heart cells with the rhythmic properties of the intact heart, we have examined slow mo (smo) , a recessive mutation we discovered in the zebrafish Danio rerio . This mutation causes a reduced heart rate in the embryo, a property we can quantitate because the embryo is transparent. We developed methods for culture of cardiocytes from zebrafish embryos and found that, even in culture, cells from smo continue to beat relatively slowly. By patch-clamp analysis, we discovered that a large repertoire of cardiac currents noted in other species are present in these cultured cells, including sodium, T-type, and L-type calcium and several potassium currents, all of which appear normal in the mutant. The only abnormality appears to be in a hyperpolarization-activated inward current with the properties of I h , a current described previously in the nervous system, pacemaker, and other cardiac tissue. smo cardiomyocytes have a reduction in I h that appears to result from severe diminution of one kinetic component of the I h current. This provides strong evidence that I h is an important contributor to the pacemaking behavior of the intact heart.
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