Wnt11 patterns a myocardial electrical gradient through regulation of the L-type Ca2+ channel

• Published in: Nature (London) 2010-08, Vol.466 (7308), p.874-878
• Main Authors: Panáková, Daniela, Werdich, Andreas A., MacRae, Calum A.
• Format: Article
• Language: English
• Subjects: 631/136; 631/443/592; 631/45/269/1146; 631/80/86/1999; Biological and medical sciences; Cell membranes. Ionic channels. Membrane pores; Cell structures and functions; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; letter; Molecular and cellular biology; multidisciplinary; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature09249

Signalling cardiac currents Many important biological processes, including the normal functioning of the heart, require an electrical gradient. The mechanisms that create and maintain such electrical polarities are poorly understood. Using techniques developed to study voltage and calcium in the developing zebrafish heart, Panáková et al . have now identified a previously unrecognized gradient of electrical coupling in the myocardial plane. The emergence of the electrical gradient depends on calcium conductance through the L-type calcium channel, which, surprisingly, is physiologically regulated by Wnt11 signalling. This work shows that electrical patterning of the embryonic heart involves an interaction between an important developmental signal and ion channels in the cell membrane — rather than relying on specialized conduction tissue. An electrical gradient is crucial for the normal functioning of the heart. These authors show that Wnt11 signals are required to set up this gradient in the developing zebrafish heart by regulating the L-type calcium channel. Electrical gradients are critical for many biological processes, including the normal function of excitable tissues, left–right patterning, organogenesis and wound healing 1 , 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 Ca 2+ conductance mediated by the L-type calcium channel. These data reveal a previously unrecognized role for Wnt/Ca 2+ 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.