Search

Catecholaminergic polymorphic ventricular tachycardia is characterized by stress-triggered syncope and sudden death. Patients with catecholaminergic polymorphic ventricular tachycardia manifest sinoatrial node (SAN) dysfunction, the mechanisms of which remain unexplored.

Xenopus oocytes have been injected with different combinations of expression plasmids carrying the rat brain alpha 1A and different beta (beta 1-4) Ca2+ channel subunit cDNAs. Whole-cell Ba2+ and Ca2+ currents were recorded up to seven days after injection. Intra-oocyte injection of BAPTA allowed us to record uncontaminated Ba2+, Sr2+ currents. The alpha 1A calcium channel showed relative current amplitudes according to the sequence: IBa2+ISr2+ICa2+. The ratio ICa2+/IBa2+ was significantly larger when compared to the class C L-type Ca2+ channel (alpha 1C). However, currents flowing through alpha 1A and alpha (1C) subunits saturate for similar Ba2+ concentrations and display the anomalous mole fraction effect in the presence of mixtures of Ba2+ and Ca2+ ions in the external medium. In oocytes expressing the alpha 1A Ca2+ channel subunit, switching from extracellular Ba2+ to Ca2+ also induced a depolarising shift of current-to-voltage relation and the steady-state inactivation curve, and increased the time-to-peak of the current. Inactivation kinetics were poorly affected. Changes in gating and voltage-dependence of activation, but not in the voltage-dependent inactivation, were independent from the coexpressed beta subunit (except with the beta 4 subunit). Our data constitute strong evidence for the existence of differences in intra-pore Ca2+ binding sites between the alpha 1C and alpha 1A subunits, and emphasise the influence of the charge carrier on the modulation of alpha 1A properties by the beta subunits.