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Early effects of parathyroid hormone on membrane potential of rat osteoblasts in culture: Role of cAMP and Ca 2+
Author(s) -
Fritsch Jeanine,
Edelman Aleksander,
Balsan Sonia
Publication year - 1988
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650030511
Subject(s) - ibmx , depolarization , endocrinology , medicine , parathyroid hormone , chemistry , forskolin , hyperpolarization (physics) , membrane potential , intracellular , biophysics , calcium , biology , biochemistry , organic chemistry , stimulation , nuclear magnetic resonance spectroscopy
Microelectrodes were used to investigate the possible involvement of cAMP and Ca 2+ ions in the parathyroid hormone's, bPTH(1–34), effect on the membrane potential of rat osteoblasts in primary culture. Parathyroid hormone (10 −7 M) depolarized cell membrane by 25.0 ± 6.1 mV (mean ± standard deviation, SD; n = 17). Blocking Ca 2+ influx with the Ca channel blocker cobalt revealed two phases in the hormone effect: a rapid and slight membrane hyperpolarization followed by sustained depolarization. In addition, cobalt significantly ( p < 0.01) decreased the magnitude of the PTH depolarizing action. The addition of dibutyryl‐cAMP (10 −3 M) to the perfusion solution also resulted in a biphasic effect. At a lower concentration (10 −4 M), dibutyryl‐cAMP produced only membrane hyperpolarization, suggesting a cAMP dose dependence of the opposite membrane potential changes. Forskolin (10 −5 M) and the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) (10 −4 M) mimicked the depolarizing effect of PTH. IBMX at a low concentration (5 × 10 −6 M) potentiated the depolarizing effect of PTH. Increases in [Ca 2+ ] i using Ca 2+ ionophore A23187 and intracellular injection of CaCl 2 or inositol trisphosphate decreased the PTH depolarizing action, whereas intracellular injection of EGTA enhanced this effect. These results indicate that PTH evokes a biphasic change in rat osteoblast membrane potential that seems to be mediated by an increase in cAMP and modulated by intracellular calcium.