Abstract 16994: Excitation-Contraction Coupling in a Rat Model of Heart Failure With Preserved Ejection Fraction (HFpEF)

The fundamental characteristics of calcium cycling are poorly characterized in heart failure with preserved ejection fraction (HFpEF). Abnormal diastolic function is the hallmark of HFpEF, but several lines of evidence hint that systolic function is also defective. To characterize excitation-contraction (EC) coupling in HFpEF, we measured L-type Ca current (ICa) and intracellular calcium (Ca) in left ventricular myocytes isolated from Dahl salt-sensitive (DS) rats with phenotypically-verified HFpEF produced by feeding them a high salt diet (8% NaCl). DS rats fed normal salt served as controls (Con). Whole-cell patch clamp revealed a 24% increase in ICa density in HFpEF myocytes depolarized to 0 mV (n=17 Con; n=29 HFpEF; p<0.01) with a leftward shift in the peak voltage, despite a 37% reduction in Cav1.2 protein expression by mass spectroscopy. ICa inactivation kinetics were slowed in HFpEF (τfast: 7.2 ± 0.4 vs. 9.0 ± 0.7, p<0.03; τslow: 59.8 ± 2.8 vs. 86.8 ± 5.8, p<0.001; n=20 Con, n=17 HFpEF). Steady-sta...