Increased Risk for Atrial Alternans in Rabbit Heart Failure: The Role of Ca/Calmodulin-Dependent Kinase II and Inositol-1,4,5-trisphosphate Signaling.

Heart failure (HF) increases the probability of cardiac arrhythmias, including atrial fibrillation (AF), but the mechanisms linking HF to AF are poorly understood. We investigated disturbances in Ca signaling and electrophysiology in rabbit atrial myocytes from normal and failing hearts and identified mechanisms that contribute to the higher risk of atrial arrhythmias in HF. Ca transient (CaT) alternans-beat-to-beat alternations in CaT amplitude-served as indicator of increased arrhythmogenicity.

Activation of small conductance Ca -activated K channels suppresses Ca transient and action potential alternans in ventricular myocytes.

At the cellular level, cardiac alternans is observed as beat-to-beat alternations in contraction strength, action potential (AP) morphology and Ca transient (CaT) amplitude, and is a risk factor for cardiac arrhythmia. The (patho)physiological roles of small conductance Ca -activated K (SK) channels in ventricles are poorly understood. We tested the hypothesis that in single rabbit ventricular myocytes pharmacological modulation of SK channels plays a causative role for the development of pacing-induced CaT and AP duration (APD) alternans.

Mechanism of carvedilol induced action potential and calcium alternans.

Carvedilol is a nonspecific β-blocker clinically used for the treatment of cardiovascular diseases but has also been shown to have profound effects on excitation-contraction coupling and Ca signaling at the cellular level. We investigate the mechanism by which carvedilol facilitates Ca transient (CaT) and action potential duration (APD) alternans in rabbit atrial myocytes. Carvedilol lowered the frequency threshold for pacing-induced CaT alternans and facilitated alternans in a concentration-dependent manner.

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.