EFFECT OF CALCIUM AND CAMP ON GO-ALPHA EXPRESSION IN NEONATAL RAT CARDIAC MYOCYTES

Culturing neonatal rat cardiac myocytes in 50 mM KCl inhibits the accumulation of G(o-alpha) that occurs when myocytes are placed in culture. The mechanism by which high extracellular K+ inhibits G(o-alpha) accumulation in myocytes was investigated by measurement of the concentration of intracellular Ca2+ ([Ca2+]) and adenosine 3',5'-cyclic monophosphate concentration ([cAMP]) of control and K+-depolarized myocytes. Although intracellular [Ca2+] in K+-depolarized myocytes was twofold higher than basal intracellular [Ca2+] in control cells, the mean intracellular [Ca2+] in contracting control myocytes was comparable to that of K+-depolarized myocytes. Furthermore, myocytes cultured in low Ca2+ plus high K+ exhibited an inhibition of G(o-alpha) accumulation, even though intracellular [Ca2+] was 10-fold lower than that of cells cultured in normal Ca2+ plus high K+. In addition, intracellular [cAMP] of K+-depolarized myocytes was comparable to that of control cells. Moreover, dibutyryl cAMP inhibited G(o-alpha) accumulation in myocytes to the same extent as high K+, even though intracellular [cAMP] differed 10-fold. Thus neither intracellular Ca2+ nor cAMP appear to mediate the inhibitory effect of high K+ on G(o-alpha) accumulation. However, cAMP has an inhibitory effect on G(o-alpha) expression that is independent of K+.