很多重要生物过程,包括心脏的正常功能,都需要一个电梯度。人们对产生和维持这种电极性的机制很不了解。现在,Panáková等人利用开发用来研究发育中的斑马鱼心脏中电压和钙的方法,识别出心肌平面中电耦合的一个以前未被认识到的梯度。
这个电梯度的出现取决于通过L-型钙通道的钙电导,而出人意料的是,这个通道在生理上是由Wnt11信号作用调控的。这项工作表明,胚胎心脏的电模式形成涉及细胞膜中一个重要发育信号和离子通道之间的互动,而不是依赖于专门化的导电组织。(生物谷Bioon.com)
生物谷推荐原文出处:
Nature doi:10.1038/nature09249
Wnt11 patterns a myocardial electrical gradient through regulation of the L-type Ca2+ channel
Daniela Panáková,Andreas A. Werdich& Calum A. MacRae
Electrical gradients are critical for many biological processes, including the normal function of excitable tissues, left–right patterning, organogenesis and wound healing1, 2, 3, 4. The fundamental mechanisms that regulate the establishment and maintenance of such electrical polarities are poorly understood. Here we identify a gradient of electrical coupling across the developing ventricular myocardium using high-speed optical mapping of transmembrane potentials and calcium concentrations in the zebrafish heart. We excluded a role for differences in cellular excitability, connexin localization, tissue geometry and mechanical inputs, but in contrast we were able to demonstrate that non-canonical Wnt11 signals are required for the genesis of this myocardial electrical gradient. Although the traditional planar cell polarity pathway is not involved, we obtained evidence that Wnt11 acts to set up this gradient of electrical coupling through effects on transmembrane Ca2+ conductance mediated by the L-type calcium channel. These data reveal a previously unrecognized role for Wnt/Ca2+ signalling in establishing an electrical gradient in the plane of the developing cardiac epithelium through modulation of ion-channel function. The regulation of cellular coupling through such mechanisms may be a general property of non-canonical Wnt signals.