Abstract
Membrane potential has a major influence on stimulus-secretion coupling in various excitable cells. The role of membrane potential in the regulation of parathyroid hormone secretion is not known. High K+-induced depolarization increases secretion from parathyroid cells. The paradox is that increased extracellular Ca2+, which inhibits secretion, has also been postulated to have a depolarizing effect. In this study, human parathyroid cells from parathyroid adenomas were used in patch clamp studies of K+ channels and membrane potential. Detailed characterization revealed two K+ channels that were strictly dependent of intracellular Ca2+ concentration. At high extracellular Ca2+, a large K+ current was seen, and the cells were hyperpolarized (-50.4 +/- 13.4 mV), whereas lowering of extracellular Ca2+ resulted in a dramatic decrease in K+ current and depolarization of the cells (-0.1 +/- 8.8 mV, p < 0.001). Changes in extracellular Ca2+ did not alter K+ currents when intracellular Ca2+ was clamped, indicating that K+ channels are activated by intracellular Ca2+. The results were concordant in cell-attached, perforated patch, whole-cell and excised membrane patch configurations. These results suggest that [Ca2+]o regulates membrane potential of human parathyroid cells via Ca2+-activated K+ channels and that the membrane potential may be of greater importance for the stimulus-secretion coupling than recognized previously.
Highlights
Extracellular free calcium ([Ca2ϩ]o) regulates the secretion of parathyroid hormone (PTH)1 from parathyroid cells through a cell surface Ca2ϩ-sensing receptor (CaR) [1,2,3]
Human parathyroid cells from parathyroid adenomas were used in patch clamp studies of K؉ channels and membrane potential
The results were concordant in cell-attached, perforated patch, whole-cell and excised membrane patch configurations. These results suggest that [Ca2؉]o regulates membrane potential of human parathyroid cells via Ca2؉-activated K؉ channels and that the membrane potential may be of greater importance for the stimulussecretion coupling than recognized previously
Summary
Extracellular free calcium ([Ca2ϩ]o) regulates the secretion of parathyroid hormone (PTH) from parathyroid cells through a cell surface Ca2ϩ-sensing receptor (CaR) [1,2,3]. The second messenger mediating the inhibition is the free intracellular Ca2ϩ ([Ca2ϩ]i) [4] In this respect, the parathyroid cell differs from the majority of other endocrine cells, in which secretion is stimulated by high [Ca2ϩ]i. At low [Ca2ϩ]i, only a small Kϩ current could be detected, and the cells were depolarized, whereas elevation of [Ca2ϩ]i resulted in dramatic enhancement of Kϩ current, and the cells were hyperpolarized. Taken together, these findings demonstrate that extracellular Ca2ϩ regulates membrane potential of human parathyroid cells via Ca2ϩ-activated Kϩ channels
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