The spontaneous electrical activity of calcitonin-secreting cells (C-cells) appears to play an important role in the coupling of fluctuations in the extracellular Ca2+ to changes in the intracellular Ca2+ concentration and thus for calcitonin secretion. Using the patch clamp technique, we have investigated the spontaneous electrical activity and the underlying ionic currents in C-cells of the rMTC 44-2 cell line. With 1.2 mM external Ca2+, the membrane potential was -46.1 +/- 1.7 mV (n = 58) and about 30% of the cells spontaneously fired action potentials. Rising the external Ca2+ to 1.8 mM caused the cells to depolarize to -42.1 +/- 2.1 mV (n = 56) and spontaneous electrical activity was seen in about 70% of cells. Under voltage clamp conditions, tetrodotoxin-sensitive voltage-dependent Na+ currents, outward-rectifying K+ currents and isradipine-, omega-conotoxin-sensitive as well as isradipine- and omega-conotoxin-insensitive Ca2+ currents were observed. These voltage-dependent currents appear to be the major ionic currents contributing to action potentials in C-cells and to participate in calcitonin secretion.