A slowly inactivating calcium current works as a calcium sensor in calcitonin-secreting cells.
Calcitonin (CT)-secreting cells (C-cells) are remarkably sensitive to changes in the extracellular Ca2+ concentration. In order to detect the mechanism by which C-cells monitor Ca2+, we compared a C-cell line responding to Ca2+ (rMTC cells) with another one known to have a defect in this Ca2+ signal transduction (TT cells). Rises of the Ca2+ concentration caused rMTC cells to depolarize and/or elicited spontaneous action potentials. Under voltage-clamp conditions, rMTC cells showed a slowly decaying Ca2+ inward current which was sensitive to dihydropyridines but not to Ni2+ at a low concentration. In contrast, the 'defective' TT cells neither depolarized nor fired action potentials with high Ca2+; they only exhibited an Ni2(+)-sensitive, transient Ca2+ current. The data strongly suggest that the slowly inactivating Ca2+ current is a prerequisite for Ca2(+)-sensitivity of C-cells and that fast inactivating channels are not sufficient to act as sensors of the extracellular Ca2+ concentration.
Pharmakologisches Institut der Freien Universität Berlin, FRG.
H
H
Scherübl
G
G
Schultz
J
J
Hescheler
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002116:Calcitonin / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D015220:Calcium Channels; D001464:Barium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002116:Calcitonin; D002118:Calcium