Time- and subunit-dependent differential mRNA expression of L-type Ca2+ channel during progression of right...

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 alpha1c and auxiliary subunits (alpha2delta, beta2 and beta3) 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, alpha1c 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 alpha2delta mRNA showed a pattern similar to that of alpha1c. The beta3 mRNA increased rapidly after monocrotaline injection and increased approximately 4.1 fold. On the other hand, beta2 mRNA showed no significant changes. Accordingly, only the mRNA ratio of beta3 to alpha1c 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 alpha1c 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.