Two distinct Na+ currents control cytosolic Ca2+ pulsing in Xenopus laevis pituitary melanotrophs

Studies with the Na+ channel blocker tetrodotoxin (TTx) on Ca(2+)-dependent hormone release by mammalian and amphibian pituitary melanotrophs have suggested that the Na+ spikes these cells generate are not responsible for triggering Ca2+ influx and consequently secretion. In contrast, we found in Xenopus laevis melanotrophs that the spontaneously occurring elevations in cytosolic free Ca2+ concentration ("Ca2+ pulses') were dependent on the presence of extracellular Na+ and sensitive to TTx and the Na+ channel activator, veratridine. However, an inhibitory effect of TTx could only be demonstrated when the extracellular Na+ concentration was lowered to near-threshold levels. In voltage-clamp experiments, two distinct Na+ currents were recorded, one sensitive to TTx and the other insensitive to TTx but blocked by micromolar concentrations of Cd2+. Together they appeared to control action potential activity and spontaneous Ca2+ pulsing. These data strongly suggest that Na+ action potentials do regulate cytosolic free Ca2+ concentration in melanotrophs.