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.
Valentijn
J A
JA
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Valentijn
K
K
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D005470:Fluorometry / Q000379:methods; D008297:Male; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D014982:Xenopus laevis / Q000502:physiology*
D015222:Sodium Channels; D002104:Cadmium; D013779:Tetrodotoxin; D014701:Veratridine; D002118:Calcium