Wnt11 patterns a myocardial electrical gradient via regulation of the L-type Ca(2+) channel

Electrical gradients are critical for many biological processes, including the normal function of excitable tissues, left-right patterning, organogenesis, and wound healing1–4. The fundamental mechanisms that regulate the establishment and maintenance of such electrical polarities are poorly understood. Using high-speed optical mapping of transmembrane potentials and calcium concentrations in the zebrafish heart, we have identified a gradient of electrical coupling across the developing ventricular myocardium. We excluded a role for 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. Importantly, though 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 via the L-type calcium channel. These data reveal a previously unrecognized role for Wnt/Ca(2+) signaling in establishing an electrical gradient in the plane of 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.