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- Title
Cytosolic Cl<sup>−</sup> ions in the regulation of secretory and endocytotic activity in melanotrophs from mouse pituitary tissue slices.
- Authors
Turner, Jan-Eric; Sedej, Simon; Rupnik, Marjan
- 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-γ-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.
- Subjects
ENDOCRINE glands; CELLS; CALCIUM channels; PATCH-clamp techniques (Electrophysiology); EXOCYTOSIS; G proteins
- Publication
Journal of Physiology, 2005, Vol 566, Issue 2, p443
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/jphysiol.2005.088997