Expression of Calcium Channels in Adult Cardiac Myocytes is Regulated by Calcium

In addition to playing a significant role in cardiac excitation–contraction coupling, intracellular Ca2+([Ca2+]i) can regulate gene expression. While the mechanisms regulating expression of Ca2+channels are not entirely defined, some evidence exists for Ca2+-dependent regulation. Using an adult ventricular myocyte culture system, we determined the effects of Ca2+on: (1) abundance of mRNA for -type Ca2+channelα1subunit (DHP receptor); (2) amount of DHP receptors; and (3) whole-cell Ca2+current (ICa). Rat ventricular myocytes were cultured for 1–3 days in serum-free medium containing either normal (1.8 m ) or high (4.8 m ) Ca2+. Exposing myocytes to high Ca2+rapidly elevated [Ca2+]ias determined by fura-2. Northern blot analysis revealed that culturing cells in high Ca2+produced 1.5-fold increase in mRNA levels for the DHP receptor. The abundance of DHP receptors, determined by ligand binding, was two-fold greater in myocytes after 3 days in high Ca2+. Moreover, peak ICawas larger in myocytes cultured for 3 days in high Ca2+(−17.8±1.5 pA/pF,n=26) than in control cells (−11.0±1.0 pA/pF,n=23). Voltage-dependent activation and inactivation, rates of current decay, as well as percent increases in ICaelicited by Bay K8644 were similar in all groups. Therefore, larger ICais likely to represent a greater number of functional channels with unchanged kinetics. Our data support the conclusion that transient changes in [Ca2+]ican modulate DHP receptor mRNA and protein abundance, producing a corresponding change in functional Ca2+channels in adult ventricular myocytes.