Cytosolic calcium responses of single rMTC 44-2 cells to stimulation with external calcium and potassium.
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)
Fajtova
V T
VT
Endocrine-Hypertension Unit, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Quinn
S J
SJ
Brown
E M
EM
D000818:Animals; D002116:Calcitonin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism*; D016257:Fura-2; D010280:Parathyroid Glands / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism
D002121:Calcium Channel Blockers; D010455:Peptides; D002116:Calcitonin; D011188:Potassium; D002118:Calcium; D016257:Fura-2