Genetic deletion of the alpha1D Ca2+ channel in mice resulted in atrial electrocardiographic abnormalities, vulnerability to atrial fibrillation, and a 24.5% reduction in I(Ca-L) (P<0.05).
Does genetic deletion of the alpha1D Ca2+ channel cause electrophysiological abnormalities and atrial fibrillation vulnerability in mice?
Genetic deletion of the alpha1D Ca2+ channel in mice leads to impaired intracellular Ca2+ handling, reduced L-type Ca2+ current, and increased vulnerability to atrial fibrillation.
Effect estimate: 24.5% reduction in I(Ca-L)
p-value: p=<0.05
The novel alpha1D Ca2+ channel together with alpha1C Ca2+ channel contribute to the L-type Ca2+ current (I(Ca-L)) in the mouse supraventricular tissue. However, its functional role in the heart is just emerging. We used the alpha1D gene knockout (KO) mouse to investigate the electrophysiological features, the relative contribution of the alpha1D Ca2+ channel to the global I(Ca-L), the intracellular Ca2+ transient, the Ca2+ handling by the sarcoplasmic reticulum (SR), and the inducibility of atrial fibrillation (AF). In vivo and ex vivo ECG recordings from alpha1D KO mice demonstrated significant sinus bradycardia, atrioventricular block, and vulnerability to AF. The wild-type mice showed no ECG abnormalities and no AF. Patch-clamp recordings from isolated alpha1D KO atrial myocytes revealed a significant reduction of I(Ca-L) (24.5%; P < 0.05). However, there were no changes in other currents such as I(Na), I(Ca-T), I(K), I(f), and I(to) and no changes in alpha1C mRNA levels of alpha1D KO atria. Fura 2-loaded atrial myocytes showed reduced intracellular Ca2+ transient (approximately 40%; P < 0.05) and rapid caffeine application caused a 17% reduction of the SR Ca2+ content (P < 0.05) and a 28% reduction (P < 0.05) of fractional SR Ca2+ release in alpha1D KO atria. In conclusion, genetic deletion of alpha1D Ca2+ channel in mice results in atrial electrocardiographic abnormalities and AF vulnerability. The electrical abnormalities in the alpha1D KO mice were associated with a decrease in the total I(Ca-L) density, a reduction in intracellular Ca2+ transient, and impaired intracellular Ca2+ handling. These findings provide new insights into the mechanism leading to atrial electrical dysfunction in the alpha1D KO mice.
Mancarella et al. (Sat,) conducted a other in Atrial fibrillation and electrophysiological abnormalities. Alpha1D gene knockout vs. Wild-type mice was evaluated on L-type Ca2+ current (I(Ca-L)) and intracellular Ca2+ transient (24.5% reduction in I(Ca-L), p=<0.05). Genetic deletion of the alpha1D Ca2+ channel in mice resulted in atrial electrocardiographic abnormalities, vulnerability to atrial fibrillation, and a 24.5% reduction in I(Ca-L) (P<0.05).