Depolarizing response of rat parathyroid cells to divalent cations

Abstract

Membrane potentials were recorded from rat parathyroid glands continuously perfused in vitro. At 1 .5 mM external Ca", the resting potential averages -73 ± 5 mV (mean ± SD, n = 66). On exposure to 2.5 mM Ca", the cells depolarize reversibly to a potential of -34 ± 8 mV (mean ± SD). Depolarization to this value is complete in ^-2-4 min, and repolarization on return to 1 .5 mM Ca" takes about the same time. The depolarizing action of high Ca" is mimicked by all divalent cations tested, with the following order of effectiveness: Ca" > Sr" > Mg" > Ba++ for alkali-earth metals, and Ca" > Cd++ > Mn++ > Co' > Zn++ for transition metals . Input resistance in 1 .5 mM Ca" was 24 .35 ± 14 MQ (mean ± SD) and increased by an average factor of 2.43 ± 0.8 after switching to 2.5 mM Ca++. The low value of input resistance suggests that cells are coupled by low-resistance junctions. Theresting potential in low Ca' is quite insensitive to removal of external Na+ or Cl-, but very sensitive to changes in external K+. Cells depolarize by 61 mV for a 10=fold increase in external K+. In high Ca++, membrane potential is less sensitive to an increase in external K+ and is unchanged by increasing K+ from 5 to 25 mM. Depolarization evoked by high Ca' may be slowed, but is unchanged in amplitude by removal of external Na+ or Cl-. Organic (13600) and inorganic (Co++, Cd++, and Mn++) blockers of the Ca' channels do not interfere with the electrical response to Ca" changes. Our results show remarkable parallels to previous observations on the control ofparathormone (PTH) release by Ca". They suggest an association between membrane voltage and secretion that is very unusual: parathyroid cells secrete when fully polarized, and secrete less when depolarized. The extraordinary sensitivity of parathyroid cells to divalent cations leads us to hypothesize the existence in their membranes ofa divalent cation receptor that controls membrane permeability (possibly to K+) and PTH secretion .