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Cytosolic Cl- ions in the regulation of secretory and endocytotic activity in melanotrophs from mouse pituitary tissue slices.

Authors
  • Turner, Jan-Eric
  • Sedej, Simon
  • Rupnik, Marjan
Type
Published Article
Journal
The Journal of physiology
Publication Date
Jul 15, 2005
Volume
566
Issue
Pt 2
Pages
443–453
Identifiers
PMID: 15890700
Source
Medline
License
Unknown

Abstract

Cl- ions are known regulators of Ca2+ -dependent secretory activity in many endocrine cells. The suggested mechanisms of Cl- action involve the modulation of GTP-binding proteins, voltage-activated calcium channels or maturation of secretory vesicles. We examined the role of cytosolic Cl- ([Cl-]i) and Cl- currents in the regulation of secretory activity in mouse melanotrophs from fresh pituitary tissue slices by using the whole-cell patch-clamp. We confirmed that elevated [Cl-]i augments Ca2- -dependent exocytosis and showed that Cl- acts on secretory vesicle maturation. The latter process was abolished by a V-type H- -ATPase blocker (bafilomycin), intracellular 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), a Cl- channel blocker, and tolbutamide, a sulphonylurea implicated in secretory vesicle maturation. In a small subset of cells, block of plasmalemmal Cl- current by DIDS reversibly enhanced endocytosis. The direct activation of G-proteins by GTP-gamma-S, a non-hydrolysable GTP analogue, did not restore the impaired secretion observed in low [Cl-]i conditions. The amplitude of voltage-activated calcium currents was unaffected by the [Cl-]i. Furthermore, two Cl- -permeable channels, calcium-activated Cl- channels and GABAA receptors, appeared as major regulators of intracellular Cl- homeostasis. In conclusion, the predominant underlying mechanism of Cl- action is mediated by intracellular Cl- fluxes during vesicle maturation, rather than activation of G-proteins or modulation of voltage-activated Ca2+channels.

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