title: High extracellular Ca2+ hyperpolarizes human parathyroid cells via Ca(2+)-activated K+ channels.
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.
authors.affiliation: Department of Molecular Medicine, Karolinska Hospital, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors.forename: Stiina
authors.initials: S
authors.lastname: Välimäki
authors.forename: Anders
authors.initials: A
authors.lastname: Höög
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.forename: Lars-Ove
authors.initials: LO
authors.lastname: Farnebo
authors.forename: Robert
authors.initials: R
authors.lastname: Bränström
mesh_terms: D000236:Adenoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D004594:Electrophysiology; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials; D008875:Middle Aged; D010280:Parathyroid Glands / Q000166:cytology* / Q000502:physiology*; D010281:Parathyroid Hormone / Q000737:chemistry; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry*
chemical_list: D010281:Parathyroid Hormone; D015221:Potassium Channels; D011188:Potassium; D002118:Calcium