SECRETAGOGUE-INDUCED GATING OF CHLORIDE CHANNELS IN THE SECRETORY VESICLES OF PARAFOLLICULAR CELLS

Thyroid parafollicular (PF) cells are neural crest-derived endocrine c ells that secrete serotonin and calcitonin. The secretory vesicles of PF cells acidify when secretion is induced by increased extracellular Ca2+ or TSH. We tested the hypothesis that acidification is regulated by secretogogue-gated Cl- channels in vesicular membranes. Cl- channel (p64) immunoreactivity was enriched in purified PF vesicles. X-Ray mi croanalysis showed a change in chlorine level in PF vesicles in respon se to secretogogue-stimulation of isolated cells. Secretogogue stimula tion also altered the degree of p64 channel phosphorylation. Protein k inase and phosphatase inhibitors antagonized secretogogue-induced vesi cle acidification and secretion; however, secretion could occur even w hen acidification was blocked. We conclude that acidification of PF ve sicles is regulated by a gatable Cl- channel in vesicle membranes and that protein phosphorylation and dephosphorylation are involved in cha nnel activation. Acidification of vesicles is not required for exocyto sis.