Molecular and Electrical Remodeling of L- and T-Type Ca²⁺ Channels in Rat Right Atrium With Monocrotaline-Induced Pulmonary Hypertension

Abstract

Background Atrial arrhythmia is often encountered in chronic pulmonary disease with pulmonary hypertension (PH), but few studies have investigated the electrical remodeling of atrial Ca²⁺ channels under PH. Methods and Results Wistar rats were injected with monocrotaline (MCT), resulting in PH with right atrial and ventricular hypertrophy. The L-type Ca²⁺ channel current density was significantly decreased in right atrial cells of MCT-treated rats, accompanied by a significant reduction in mRNA expression of the CaV1.2 (α_1C) subunit and accessory β₂ subunit. Conversely, the low voltage-activated Ca²⁺ current was more marked in the right atrial cells of MCT-treated rats than in those of control rats. The current-voltage relationship and the time course of inactivation closely resembled those of T-type Ca²⁺ channels, although the current was only slightly inhibited by 10-100 μmol/L Ni²⁺. No significant differences were observed in the mRNA expression levels of CaV3.1 (α_1G) and CaV3.2 (α_1H) or the protein level of the CaV3.1 subunit. In left atrial cells, the electrophysiological molecular properties of Ca²⁺ channels were unaffected by MCT treatment. Conclusions PH causes right atrial hypertrophy, associated with alteration of the electrophysiological molecular properties of Ca²⁺ channels. (Circ J 2009; 73: 256 - 263)