SERUM CONTAINS A POTENT FACTOR THAT DECREASES BETA-ADRENERGIC RECEPTOR-STIMULATED L-TYPE CA-2+ CURRENT IN CARDIAC MYOCYTES

L-type Ca2+ current (I(Ca)) was measured in cultured atrial myocytes from hearts of adult guinea-pigs using whole-cell voltage clamp. Potentiation of I(Ca) induced by beta-adrenergic stimulation (isoprenaline 2. 10(-7) M) could be completely antagonized by diluted sera (1:100 v/v). Half-maximal inhibition of beta-receptor-stimulated I(Ca) occurred at about 1:1000. Basal I(Ca) was not affected by serum. Atropine in a concentration (10(-6) M) that completely antagonized the anti-adrenergic effect of acetylcholine (ACh, 2.10(-6) M) did not interfere with the effect of serum. In cells dialysed with cyclic adenosine monophosphate (cAMP)-containing (10(-4) M) pipette solution, potentiated I(Ca) was insensitive to both ACh and serum. Preincubation of the myocytes with pertussis toxin almost completely abolished the anti-adrenergic effects of both ACh and serum. The potency of serum was not reduced by dialysis. It is concluded that serum contains a factor which, like ACh, inhibits beta-receptor-stimulated adenylyl cyclase via G(i)-protein.