Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Turner, JE; Sedej, S; Rupnik, M.
Cytosolic Cl- ions in the regulation of secretory and endocytotic activity in melanotrophs from mouse pituitary tissue slices.
J Physiol. 2005; 566(Pt 2):443-453
Doi: 10.1113/jphysiol.2005.088997
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- Führende Autor*innen der Med Uni Graz
- Sedej Simon
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- 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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- Algorithms -
- Animals -
- Calcium - metabolism
- Calcium Signaling - physiology
- Cell Membrane - metabolism
- Chlorides - metabolism
- Cytosol - metabolism
- Electrophysiology - metabolism
- Endocytosis - physiology
- Exocytosis - physiology
- Male - physiology
- Melanins - metabolism
- Membrane Potentials - physiology
- Mice - physiology
- Patch-Clamp Techniques - physiology
- Pituitary Gland - cytology
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