Spectrin-based pathways for regulation of cardiac excitability
Recent efforts from the Hund lab have focused on novel roles for the actin-associated protein βIV-spectrin in organizing ion channel macromolecular complexes in heart. While previous studies were restricted to brain, we have identified a critical role for βIV-spectrin in organizing specific ion channel regulatory complexes at the cardiomyocyte intercalated disc.
Hund TJ, Koval OM, Li J, Wright PJ, Qian L, Snyder JS, Gudmundsson H, Kline CF, Davidson NP, Cardona N, Rasband MN, Anderson ME, and Mohler PJ. A betaIV spectrin/CaMKII signaling complex is essential for membrane excitability in mice. J Clin Invest. 2010; 120:3508-19. PMCID: PMC2947241.
Hund TJ, Snyder JS, Wu X, Glynn P, Koval OM, Onal B, Leymaster ND, Unudurthi SD, Curran J, Camardo C, Wright PJ, Binkley PF, Anderson ME, Mohler PJ. βIV-spectrin regulates TREK-1 membrane targeting in heart. Cardiovasc Res. 2014; 102:166-75. PMCID:PMC3958619.
Smith SA, Sturm AC, Curran J, Kline CF, Little SC, Bonilla IM, Long VP, Makara M, Polina I, Hughes LD, Webb TR, Wei Z, Wright P, Voigt N, Bhakta D, Spoonamore KG, Zhang C, Weiss R, Binkley PF, Janssen PM, Kilic A, Higgins RS, Sun M, Ma J, Dobrev D, Zhang M, Carnes CA, Vatta M, Rasband MN, Hund TJ, Mohler PJ. Dysfunction in the βII spectrin-dependent cytoskeleton underlies human arrhythmia. Circulation. 2015; 131:695-708. PMCID:PMC4342332
Unudurthi SD, Wu X, Qian L, Amari F, Onal B, Li N, Makara MA, Smith SA, Snyder J, Fedorov VV, Coppola V, Anderson ME, Mohler PJ, Hund TJ. Two-pore K+ channel TREK-1 regulates sinoatrial node membrane excitability. J Am Heart Assoc. 2016; 5:e002865. PMCID:PMC4859279.