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Updated: Jun 27, 2025

Patch Clamp and Perfusion Techniques for Studying Ion Channels Expressed in Xenopus oocytes
Published on: January 10, 2011
Popeye domain containing proteins modulate the voltage-gated cardiac sodium channel Nav1.5
Susanne Rinné1, Aytug K Kiper1, Ralf Jacob2
1Institute for Physiology and Pathophysiology, Vegetative Physiology, Philipps-University of Marburg, 30537 Marburg, Germany.
None:
Popeye domain containing (POPDC) proteins are predominantly expressed in the heart and skeletal muscle, modulating the K2P potassium channel TREK-1 in a cAMP-dependent manner. POPDC1 and POPDC2 variants cause cardiac conduction disorders with or without muscular dystrophy. Searching for POPDC2-modulated ion channels using a functional co-expression screen in Xenopus oocytes, we found POPDC proteins to modulate the cardiac sodium channel Nav1.5. POPDC proteins downregulate Nav1.5 currents in a cAMP-dependent manner by reducing the surface expression of the channel. POPDC2 and Nav1.5 are both expressed in different regions of the murine heart and consistently POPDC2 co-immunoprecipitates with Nav1.5 from native cardiac tissue. Strikingly, the knock-down of popdc2 in embryonic zebrafish caused an increased upstroke velocity and overshoot of cardiac action potentials. The POPDC modulation of Nav1.5 provides a new mechanism to regulate cardiac sodium channel densities under sympathetic stimulation, which is likely to have a functional impact on cardiac physiology and inherited arrhythmias.
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