Intracellular transduction mechanism on the extracellular Ca^<2+>-sensing in parathyroid cells

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Extracellular Ca^<2+> regulates the secretion of PTH from mammalian parathyroid cells through extracellular Ca^<2+>-sensing receptor(CaR). The transduction mechanism on the Ca^<2+>-sensing was investigated using the electrophysiological technique. Parathyroid cells were isolated from the parathyroid glands of bullfrogs. Under whole-cell mode with standard K^+ internal solution, frog parathyroid cells displayed resting potential of -30±2 mV (N=44). The mean input resistance and membrane capacitance were 13.7±0.9 GΩ and 7.6±0.2 pF, respectively. After attaining the whole-cell configuration in normal saline solution, almost all frog parathyroid cells displayed transient inward currents in response to depolarizing voltage steps from a holding potential of -84 mV. The inward currents disappeared by the replacement of external Na^+ with NMDG^+ and were reversibly inhibited by TTX, indicating that the currents occur through the TTX-sensitive voltage-gated Na^+ channels. When external Ca^<2+> level was increased from 1.8 to 10 mM, the parathyroid cells displayed a large increase in conductance. The reversal potential of the response shifted according to internal Cl^- concentration. The dialysis of 0.8 mM Ca^<2+> into the cells also induced niflumic acid-sensitive conductance. The extracellular Ca^<2+>-induced currents were strongly inhibited by external Gd^<3+> and intracellular U-73122. Intracellular dialysis of IP_3 did not elicit any response in the parathyroid cells, but the dialysis of ETYA induced large inward currents. The results suggest that extracellular Ca^<2+> rise elicits Ca^<2+>-activated Cl^- conductance in frog parathyroid cells through the arachidonic acid cascade.