Regulation of Ca(2+)-conducting currents in parathyroid cells by extracellular Ca(2+) and channel blockers

Abstract

High extracellular Ca2+ concentrations ([Ca2+]o) produce sustained intracellular Ca2+ responses in parathyroid cells that correlate with suppression of parathyroid hormone release. Using whole cell patch clamping, we identified two types of Ca(2+)-conducting currents in these cells. Type 1 currents were enhanced by raising [Ca2+]o and blocked by Cd2+ and nifedipine, whereas type 2 currents were resistant to blockade by these agents. Both types of membrane currents were cation nonselective, voltage independent over a broad range of membrane potentials, and blocked by the trivalent ions La3+ and Gd3+ (> 98%). Cd2+, La3+, and Gd3+ had biphasic effects on membrane conductance (Gm). At submicromolar concentrations, these ions increased Gm, whereas at higher concentrations they reduced Gm. In contrast to ionic channel blockers, nifedipine had only an inhibitory effect on the Ca(2+)-conducting currents that were sensitive to changes in [Ca2+]o (dose inhibiting 50% of maximal response = approximately 3-10 x 10(-8) M). Microfluorimetric ratio-imaging analysis of single parathyroid cells loaded with fura 2 showed that Gd3+ inhibited sustained intracellular Ca2+ responses to high [Ca2+]o. These findings suggest that the Ca(2+)-conducting currents identified in these studies may play a role in regulating intracellular Ca2+ responses in this system.