Increased Sarcoplasmic Reticulum Calcium Leak but Unaltered Contractility by Acute CaMKII Overexpression in Isolated Rabbit Cardiac Myocytes

The predominant cardiac Ca/calmodulin-dependent protein kinase (CaMK) is CaMKIIδ. Here we acutely overexpress CaMKIIδC using adenovirus-mediated gene transfer in adult rabbit ventricular myocytes. This circumvents confounding adaptive effects in CaMKIIδC transgenic mice. CaMKIIδC protein expression and activation state (autophosphorylation) were increased 5- to 6-fold. Basal twitch contraction amplitude and kinetics (1 Hz) were not changed in CaMKIIδC versus LacZ expressing myocytes. However, the contraction–frequency relationship was more negative, frequency-dependent acceleration of relaxation was enhanced (τ0.5Hz/τ3Hz=2.14±0.10 versus 1.87±0.10), and peak Ca current (ICa) was increased by 31% (−7.1±0.5 versus −5.4±0.5 pA/pF, P