Time- and Subunit-dependent Differential mRNA Expression of L-type Ca²⁺ Channel during Progression of Right Ventricular Hypertrophy

Abstract

To clarify the molecular basis for changes in L-type calcium channel (VLCC) density in ventricular hypertrophy, we analyzed the mRNA expression of all the subunits including the main subunit α1c and auxiliary subunits (α2δ, β2 and β3) composing VLCC in rat right ventricular hypertrophy (RVH) induced by monocrotaline injection. To test the hypothesis that the expression of each subunit might change differently during progression of RVH, leading to an altered electrophysiologic outcome for VLCC, we investigated the ratio of the mRNA level of each auxiliary subunit to the main subunit. After monocrotaline injection, α1c mRNA showed a transient decrease on the 14th day and thereafter significantly increased to reach approximately 1.8 fold that of the control level on the 21st day. The auxiliary subunit α2δ mRNA showed a pattern similar to that of α1c. The β3 mRNA increased rapidly after monocrotaline injection and increased approximately 4.1 fold. On the other hand, β2 mRNA showed no significant changes. Accordingly, only the mRNA ratio of β3 to α1c showed a significant increase among the auxiliary subunits after the monocrotaline injection. The ratio increased to a maximum of approximately 5.7 fold on the 14th day and thereafter decreased. These results suggest that VLCC density may be modified not only by α1c but also by its auxiliary subunit expression in ventricular hypertrophy, and provide a clue for understanding the controversial electrophysiologic results on VLCC density in hypertrophied hearts.