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 f rom hearts of adult guinea-pigs using whole-cell voltage clamp. Potent iation 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-adrenerg ic effect of acetylcholine (ACh, 2.10(-6) M) did not interfere with th e effect of serum. In cells dialysed with cyclic adenosine monophospha te (cAMP)-containing (10(-4) M) pipette solution, potentiated I(Ca) wa s insensitive to both ACh and serum. Preincubation of the myocytes wit h pertussis toxin almost completely abolished the anti-adrenergic effe cts of both ACh and serum. The potency of serum was not reduced by dia lysis. It is concluded that serum contains a factor which, like ACh, i nhibits beta-receptor-stimulated adenylyl cyclase via G(i)-protein.