L-type Ca Channel Recovery from Inactivation in Rabbit Atrial Myocytes

Adaptation of the myocardium to varying workloads critically depends on the recovery from inactivation (RFI) of L-type Ca channels (LCCs) which provide the trigger for cardiac contraction. The goal of the present study was a comprehensive investigation of LCC RFI in atrial myocytes. The study was performed on voltage-clamped rabbit atrial myocytes using a double pulse protocol with variable diastolic intervals in cells held at physiological holding potentials, with intact intracellular Ca release, and preserved Na current and Na /Ca exchanger (NCX) activity. We demonstrate that the kinetics of RFI of LCCs are co-regulated by several factors including resting membrane potential, [Ca ] , Na influx, and activity of CaMKII. In addition, activation of CaMKII resulted in increased I amplitude at higher pacing rates. Pharmacological inhibition of NCX failed to have any significant effect on RFI, indicating that impaired removal of Ca by NCX has little effect on LCC recovery. Finally, RFI of intracellular Ca release was substantially slower than LCC RFI, suggesting that inactivation kinetics of LCC do not significantly contribute to the beat-to-beat refractoriness of SR Ca release. The study demonstrates that CaMKII and intracellular Ca dynamics play a central role in modulation of LCC activity in atrial myocytes during increased workloads that could have important consequences under pathological conditions such as atrial fibrillations, where Ca cycling and CaMKII activity are altered.