EFFECT OF LOW-DENSITY LIPOPROTEINS, MEVINOLIN, AND G-PROTEINS ON CA2+RESPONSE IN CULTURED CHICK ATRIAL CELLS

Growth of cells from atria of embryonic chick hearts 14 days in ovo in medium supplemented with lipoprotein-depleted serum (LPDS) results in an increase in total cell cholesterol, enhanced parasympathetic respo nsiveness (7), and decreased sympathetic responsiveness (1). These eff ects were reversed by the hydroxymethyl glutaryl CoA reductase inhibit or, mevinolin. In these studies, comparison of cell growth in medium s upplemented with fetal calf serum (FCS) and LPDS demonstrated that, af ter growth with LPDS, the ability of Ca2+ and the Ca2+ channel agonist , BAY K 8644, to enhance the amplitude of contraction decreased by 25 and 50%, respectively. These effects of growth in LPDS were reversed b y incubation with mevinolin. LPDS had no effect on either Ca2+ channel number as measured by (+)-[5-methyl-H-3]PN200-110 binding or Ca2+ cur rent density as measured by the whole cell patch method. Treatment of cells grown in LPDS with pertussis toxin, which inactivates alpha(o) a nd alpha(i), returned the contractile response to 10(-7) M BAY K 8644 to control levels. Pertussis toxin had no effect on the contractile re sponse or adenosine 3',5'-cyclic monophosphate levels in control cells grown in FCS alone. These data suggest that alterations in the relati ve levels of alpha(o) and alpha(s) in cells grown in LPDS may play a r ole in regulating the contractile response to Ca2+ channel agonists an d to exogenous Ca2+.