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  • Popeye domain containing proteins modulate the voltage-gated cardiac sodium channel Nav1.5.

Popeye domain containing proteins modulate the voltage-gated cardiac sodium channel Nav1.5.

iScience (2024-05-01)
Susanne Rinné, Aytug K Kiper, Ralf Jacob, Beatriz Ortiz-Bonnin, Roland F R Schindler, Sabine Fischer, Marlene Komadowski, Emilia De Martino, Martin K-H Schäfer, Tamina Cornelius, Larissa Fabritz, Christian S M Helker, Thomas Brand, Niels Decher
ABSTRACT

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.

MATERIALS
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Product Description

Sigma-Aldrich
Anti-POPDC2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution