A slowly inactivating calcium current works as a calcium sensor in calcitonin‐secreting cells

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Abstract
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.