PARATHYROID-HORMONE INCREASES CYTOSOLIC CALCIUM-CONCENTRATION IN ADULT-RAT CARDIAC MYOCYTES

The heart is a target organ for parathyroid hormone (PTH), and the act ion of this hormone on the myocardium may be mediated through the abil ity of PTH to increase cytosolic calcium ([Ca2+]i) in the myocardial c ells. However, direct evidence for such an effect of PTH is lacking, a nd the mechanism(s) through which the hormone can potentially exert su ch an effect have not been elucidated. In the present study these ques tions were examined using cardiac myocytes isolated from adult rats. B oth PTH-(1-34) and PTH(1-84) produced a dose-dependent increase in [Ca 2+]i of myocytes, but the effect of the latter was significantly (P < 0.01) greater than the former. This action of PTH was abolished by the inactivation of the hormone, the use of a PTH antagonist, or by verap amil. The G protein activator, guanosine 5'-O-(3-thiothriphosphate) (G TPgammaS), mimicked the effect of PTH, whereas pertussis toxin, the G protein inhibitor, guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS), or r yanodine significantly reduced the PTH-induced rise in [Ca2+]i. Dibuty ryl- and 8-bromoadenosine-3',5'-cyclic monophosphate, forskolin, 12-O- tetradecanoylphorbol 13-acetate, and staurosporine did not increase [C a2+], in myocytes, and staurosporine did not alter the PTH-induced ris e in [Ca2+]i. BAY K 8644 augmented the effect of PTH on [Ca2+]i. These data demonstrate that 1) PTH increases [Ca2+], of cardiac myocytes, 2 ) this action is receptor mediated and is produced by activation of th e L-type calcium channels following stimulation of G protein(s), and 3 ) the rise in [Ca2+]i is due to both augmented entry of calcium into t he myocytes and mobilization of calcium from sarcoplasmic reticulum by a calcium-induced calcium release mechanism.