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L30a Mutation Of Phospholemman Mimics Effects Of Cardiac Glycosides On Isolated Cardiomyocytes, Ryan David Himes

Dissertations

In order to determine if mutations made to phospholemman (PLM) could increase PLM binding to the Na/K-ATPase (NKA) and cause positive inotropy we performed scanning mutagenesis of the transmembrane domain of PLM and measured FRET between each mutant and NKA. We observed increased binding to NKA for several PLM mutants compared to WT, including L27A, L30A, and I32A. In isolated cardiomyocytes, overexpression of WT PLM increased the amplitude of the Ca2+ transient compared to GFP control. Ca2+ transient amplitude was further increased by L30A PLM overexpression. L30A mutation also delayed Ca2+ extrusion and increased the duration of the cardiomyocyte contraction. …