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High extracellular Ca2+ hyperpolarizes human parathyroid cells via Ca(2+)-activated K+ channels
Stiina Välimäki1, Anders Höög, Catharina Larsson
1Department of Molecular Medicine, Karolinska Hospital, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
The Journal of Biological Chemistry
|October 3, 2003
Summary
Extracellular calcium regulates human parathyroid hormone secretion by altering cell membrane potential via calcium-activated potassium channels. This finding highlights the critical role of membrane potential in stimulus-secretion coupling.
Area of Science:
- Endocrinology
- Cell Physiology
- Molecular Biology
Background:
- Membrane potential significantly influences stimulus-secretion coupling in excitable cells.
- The specific role of membrane potential in regulating parathyroid hormone (PTH) secretion remains unclear.
- High extracellular potassium (K+) depolarization stimulates PTH secretion, yet high extracellular calcium (Ca2+), which inhibits secretion, is also thought to depolarize cells.
Purpose of the Study:
- To investigate the role of membrane potential in regulating human parathyroid hormone secretion.
- To characterize potassium (K+) channels and their regulation by extracellular calcium (Ca2+) in human parathyroid cells.
Main Methods:
- Utilized patch clamp techniques on human parathyroid cells from adenomas.
- Studied K+ channel activity and membrane potential under varying extracellular Ca2+ concentrations.
- Employed cell-attached, perforated patch, whole-cell, and excised membrane patch configurations.
Main Results:
- Identified two intracellular Ca2+-dependent K+ channels in human parathyroid cells.
- High extracellular Ca2+ resulted in hyperpolarization (-50.4 ± 13.4 mV) and large K+ currents.
- Lowering extracellular Ca2+ caused significant depolarization (-0.1 ± 8.8 mV) and reduced K+ currents, independent of intracellular Ca2+ clamping.
Conclusions:
- Extracellular Ca2+ regulates the membrane potential of human parathyroid cells through Ca2+-activated K+ channels.
- The membrane potential plays a crucial role in stimulus-secretion coupling for parathyroid hormone secretion, potentially more than previously recognized.