Two distinct Na+ currents control cytosolic Cai2+ pulsing in Xenopus laevis pituitary melanotrophs

Abstract 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 Ca 2+ influx and consequently secretion. In contrast, we found in Xenopus laevis melanotrophs that the spontaneously occurring elevations in cytosolic free Ca 2+ concentration (‘Ca 2+ 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 Cd 2+ . Together they appeared to control action potential activity and spontaneous Ca 2+ pulsing. These data strongly suggest that Na + action potentials do regulate cytosolic free Ca 2+ concentration in melanotrophs.