Upregulation Of Cam Kinase IIδ Modulates Spontaneous Ca2+ Wave Properties In A Rabbit Model Of Heart Failure

Abstract

linescanning after 488nm excitation and recording emission at 505-530nm in intact Fluo-3-loaded cardiomyocytes (2uM) at 37 C and at [Ca2þ] 1.2mM and 5.0mM. These studies showed that spontaneous wave frequency was higher at 5.0mM than 1.2mM Ca2þ. Post-MI HF cardiomyocytes had ~twice the wave frequency compared to sham-operated controls. Regular ExTr post-MI improved exercise capacity and induced reverse remodeling. ExTr also reduced the frequency of spontaneous waves at both Ca2þ 1.2mM and 5.0mM, although it did not completely normalize spontaneous Ca2þ waves. ExTr also increased the ratio between aborted and complete waves at Ca2þ 1.2mM, but not Ca2þ 5.0mM. No effects were found on spontaneous wave velocity. This suggests that ExTr partly improved the control of diastolic Ca2þ by reducing the frequency of spontaneous Ca2þ waves and by improving the ability of the cardiomyocyte to eliminate a spontaneous wave after its generation, but before its propagation. Finally, we repeated these studies in the presence of the nitric oxide synthase inhibitor L-NAME, to study the contribution of nitric oxide. This did not have any effects.