L‐type Ca2+ channel recovery from inactivation in rabbit atrial myocytes

Abstract

Abstract Adaptation of the myocardium to varying workloads critically depends on the recovery from inactivation (RFI) of L‐type Ca2+ 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 Ca2+ release, and preserved Na+ current and Na+/Ca2+ exchanger (NCX) activity. We demonstrate that the kinetics of RFI of LCCs are co‐regulated by several factors including resting membrane potential, [Ca2+]i, Na+ influx, and activity of CaMKII. In addition, activation of CaMKII resulted in increased ICa amplitude at higher pacing rates. Pharmacological inhibition of NCX failed to have any significant effect on RFI, indicating that impaired removal of Ca2+ by NCX has little effect on LCC recovery. Finally, RFI of intracellular Ca2+ 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 Ca2+ release. The study demonstrates that CaMKII and intracellular Ca2+ 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 Ca2+ cycling and CaMKII activity are altered.

Keywords

• atria
• Ca2+ channel
• Ca2+ cycling
• Ca2+/calmodulin‐dependent kinase II
• recovery from inactivation