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Am J Physiol Endocrinol Metab 275: E213-E221, 1998;
0193-1849/98 $5.00
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Vol. 275, Issue 2, E213-E221, August 1998

Regulation of extracellular calcium-activated cation currents by cAMP in parathyroid cells

Wenhan Chang, Tsui-Hua Chen, Stacy Pratt, and Dolores Shoback

Endocrine Research Unit, Department of Veterans Affairs Medical Center, Department of Medicine, University of California, San Francisco, California 94121

Parathyroid cells express Ca2+-sensing receptors that couple changes in the extracellular Ca2+ concentration ([Ca2+]o) to increases in the intracellular free Ca2+ concentration ([Ca2+]i) and to the suppression of parathyroid hormone secretion. Using whole cell patch clamping, we previously identified voltage-independent Ca2+-conducting currents in bovine parathyroid cells that increased with rising [Ca2+]o and were blocked by Cd2+ and nifedipine. Because cAMP-dependent phosphorylation regulates dihydropyridine-sensitive Ca2+ channels in other systems, we tested whether cAMP modulates these currents. At 0.7 mM Ca2+, nonselective Ca2+-conducting currents were suppressed by 30-50% when the recording pipette was perfused with cAMP. High-[Ca2+]o-induced increases in membrane currents were also abrogated. The effects of cAMP were reversible and dose dependent (3 × 10-9 to 3 × 10-3 M) and required ATP in the pipette solution. Perfusion of the cell interior with the catalytic subunit of protein kinase A mimicked the effects of cAMP, as did perfusion of the bath with the adenylate cyclase activator forskolin. These findings support the idea that cAMP-dependent phosphorylation suppresses high-[Ca2+]o-induced cation currents and may play a role in regulating ion fluxes in parathyroid cells.

parathyroid hormone secretion; nonselective cation currents; calcium receptor; dihydropyridine; calcium channel; calcium influx


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W. Chang, S. Pratt, T.-H. Chen, L. Bourguignon, and D. Shoback
Amino Acids in the Cytoplasmic C Terminus of the Parathyroid Ca2+-sensing Receptor Mediate Efficient Cell-surface Expression and Phospholipase C Activation
J. Biol. Chem., November 16, 2001; 276(47): 44129 - 44136.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
W. Chang, T.-H. Chen, S. Pratt, and D. Shoback
Amino Acids in the Second and Third Intracellular Loops of the Parathyroid Ca2+-sensing Receptor Mediate Efficient Coupling to Phospholipase C
J. Biol. Chem., June 23, 2000; 275(26): 19955 - 19963.
[Abstract] [Full Text] [PDF]


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