Intracellular Ca2+ inactivates an outwardly rectifying K+ current in human adenomatous parathyroid cells

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Abstract
We have used whole-cell patch-clamp techniques to study the conductances in the plasma membranes of human parathyroid cells. With a KCl-rich pipette solution containing Ca2+ buffered to a concentration of 0.1 μmol/l, the zero current potential was −71.1±0.5 mV (n=19) and the whole-cell current/ voltage (I/V) relation had an inwardly rectifying and an outwardly rectifying component. The inwardly rectifying current activated instantaneously on hyperpolarization of the plasma membrane to potentials more negative than −80 mV, and a semi-logarithmic plot of the reversal potential of the inward current (estimated by extrapolation from the range in which it was linear) as a function of extracellular K+ concentration ([K+]o) revealed a linear relation with a slope of 64 mV per decade change in [K+]o, which is not significantly different from the Nernstian slope, demonstrating that the current was carried by K+ ions. The conductance exhibited a square root dependence on [K+]o as has been observed for inward rectifiers in other tissues. The current was blocked by the presence of Ba2+ (1 mmol/l) or Cs+ (1.5 mmol/l) in the bath. The outwardly rectifying current was activated by depolarization of the membrane potential to potentials more positive than −20 mV. It was inhibited by replacement of pipette K+ with Cs+, indicating that it also was a K+ current: it was partially (42%) blocked when tetraethylammonium (TEA+, 10 mmol/l) was added to the bath. The outwardly rectifying, but not the inwardly rectifying K+ current, was regulated by intracellular free Ca2+ concentration ([Ca2+]i) such that increasing [Ca2+]i above 10 nmol/l inhibited the outwardly rectifying current, the half-maximum effect being seen at 1 μmol/l. Since it is known that increases in [Ca2+]o produce increases in [Ca2+]i, and that they depolarize parathyroid cells by reducing the membrane K+ conductance, we suggest that it is the reduction of the outwardly rectifying K+ conductance by increases in [Ca2+]i which is responsible for the reduction in K+ conductance seen when [Ca2+]o is increased.