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 L-type Ca2+ channel alpha(1) subunit (DHP receptor); (2) amount of DHP receptors; and (3) whole-cell Ca2+ current (I-Ca). Rat ventricular myocytes were cultured for 1-3 days in serum-free medium containing either normal (1.8 mM) or high (4.8 mM) Ca2+. Exposing myocytes to high Ca2+ rapidly elevated [Ca2+](i) as determined by fura-2. Northern blot analysis revealed that culturing cells in high Ca2+ produced similar to 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 I-Ca, was 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 I-Ca elicited by Bay K8644 were similar in all groups. Therefore, larger I-Ca, is likely to represent a greater number of functional channels with unchanged kinetics. Our data support the conclusion that transient changes in [Ca2+](i) can modulate DHP receptor mRNA and protein abundance, producing a corresponding change in functional Ca2+ channels in adult ventricular myocytes. (C) 1997 Academic Press Limited.