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AJP - Endocrinology and Metabolism, Vol 261, Issue 1 E151-E158, Copyright © 1991 by American Physiological Society
ARTICLES |
V. T. Fajtova, S. J. Quinn and E. M. Brown
Endocrine-Hypertension Unit, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Few endocrine tissues can detect changes in the extracellular Ca2+ concentration within the physiological range and modify their hormone secretion accordingly. A rat cell line of C-cell origin (rMTC 44-2) secretes calcitonin and neurotensin in response to small increases in external Ca2+. To better understand the mechanism of extracellular Ca2+ sensing in this cell type, we studied single fura-2-loaded rMTC 44-2 cells perfused with increasing concentrations of Ca2+ and K+. In the basal state (Ca2+ = 0.5 mM), cytosolic Ca2+ levels were 53 nM, with 27% of the cells having spikes or oscillations. With elevation of the external Ca2+ to between 0.5 and 4 mM, 84% of the cells showed a rapid (less than 5 s) rise in cytosolic Ca2+ to values 2- to 10-fold higher than basal levels. Most of the responding cells exhibited complex patterns of cytosolic Ca2+ fluctuations, including oscillations with frequencies varying from less than 1/min to as many as 6/min. When averaged over time, the cytosolic Ca2+ of individual cells showed a dose-dependent response with changes in external Ca2+, resembling the relationship between extracellular Ca2+ and calcitonin secretion. With continued or repeated stimulation, the spike amplitude often declined. These cytosolic Ca2+ responses were attenuated in the presence of the Ca(2+)-channel blockers cadmium and nifedipine. Cytosolic Ca2+ responses to perfusion with elevated K+ (20 mM) were similar in waveform to those seen with Ca2+ stimulation. Most cells displayed cytosolic Ca2+ changes in response to both ionic secretagogues when stimulated with external Ca2+ or K+.(ABSTRACT TRUNCATED AT 250 WORDS)
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