L‐type Ca(2+) 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(2+) 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(2+) release, and preserved Na(+) current and Na(+)/Ca(2+) exchanger (NCX) activity. We demonstrate that the kinetics of RFI of LCCs are co‐regulated by several factors including resting membrane potential, [Ca(2+)](i), Na(+) influx, and activity of CaMKII. In addition, activation of CaMKII resulted in increased I (Ca) amplitude at higher pacing rates. Pharmacological inhibition of NCX failed to have any significant effect on RFI, indicating that impaired removal of Ca(2+) by NCX has little effect on LCC recovery. Finally, RFI of intracellular Ca(2+) 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(2+) release. The study demonstrates that CaMKII and intracellular Ca(2+) 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(2+) cycling and CaMKII activity are altered.