Regulation of calcium-conducting currents in parathyroid cells by
extracellular calcium, and channel-blockers.
Chang, Wenhan, Tsui-Hua Chen, Phyllis Gardner, Dolores Shoback.
Endocrine Research Unit, Department of Medicine, Veterans Affairs
Medical Center, University of California, San Francisco, CA, 94121
and Departments of Clinical Pharmacology and Medicine, Stanford
University Medical School, Stanford, CA 94305
APStracts 2:0128E, 1995.
High extracellular Ca2+ concentrations ([Ca2+]o) produce sustained
intracellular Ca2+ responses in parathyroid cells which correlate
with suppression of PTH release. Using whole-cell patch-clamping, we
identified 2 types of Ca2+-conducting currents in these cells. Type 1
currents were enhanced by raising [Ca2+]o and blocked by Cd2+ and
nifedipine, while type 2 currents were resistant to blockade by these
agents. Both types of membrane currents were cation-nonselective,
voltage-independent over a broad range of membrane potentials, and
blocked by the trivalent ions La3+ and Gd3+ (> 98%). Cd2+, La3+,
and Gd3+ had biphasic effects on membrane conductance (Gm). At
submicromolar concentrations, these ions increased Gm, while at
higher concentrations they reduced Gm. In contrast to ionic channel
-blockers, nifedipine had only an inhibitory effect on the Ca2+
-conducting currents which were sensitive to changes in [Ca2+]o (ID50
nearly equal to 3-10 X 10-8 M). Microflurimetric ratio-imaging
analysis of single parathyroid cells loaded with Fura 2 showed that
Gd3+ inhibited sustained intracellular Ca2+ responses to high
[Ca2+]o. These findings suggest that the Ca2+-conducting currents
identified in these studies may play an role in regulating
intracellular Ca2+ responses in this system.
Received 30 November 1994; accepted in final form 26 May 1995.
APS Manuscript Number E498-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.