Store-operated influx of Ca 2+ in the pancreatic β-cells exhibits graded dependence on the filling of the endoplasmic reticulum [Elektronisk resurs]

• The store-operated pathway for Ca 2+ entry was studied in individual mouse pancreatic β-cells by measuring the cytoplasmic concentrations of Ca 2+ ([Ca 2+ ] i ) and Mn 2+ ([Mn 2+ ] i ) with the fluorescent indicator fura-2. Influx through the store-operated pathway was initially shut off by pre-exposure to 20 mM glucose, which maximally stimulates intracellular Ca 2+ sequestration. To avoid interference with voltage-dependent Ca 2+ entry the cells were hyperpolarized with diazoxide and the channel blocker methoxyverapamil was present. Activation of the store-operated pathway in response to Ca 2+ depletion of the endoplasmic reticulum was estimated from the sustained elevation of [Ca 2+ ] i or from the rate of increase in [Mn 2+ ] i due to influx of these extracellular ions. Increasing concentrations of the inositol 1,4,5-trisphosphate-generating agonist carbachol or the sarco(endo)plasmatic reticulum Ca 2+ -ATPase inhibitor cyclopiazonic acid (CPA) cause gradual activation of the store-operated pathway. In addition, the carbachol- and CPA-induced influx of Mn 2+ depended on store filling in a graded manner. The store-operated influx of Ca 2+ /Mn 2+ was inhibited by Gd 3+ and 2-aminoethoxydiphenyl borate but neither of these agents discriminated between store-operated and voltage-dependent entry. The finely tuned regulation of the store-operated mechanisms in the β-cell has direct implications for the control of membrane potential and insulin secretion. 

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Medical and Health Sciences  (hsv)

Basic Medicine  (hsv)

Cell and Molecular Biology  (hsv)

Medicin och hälsovetenskap  (hsv)

Medicinska grundvetenskaper  (hsv)

Cell- och molekylärbiologi  (hsv)

MEDICINE  (svep)

Morphology, cell biology, pathology  (svep)

Cell biology  (svep)

MEDICIN  (svep)

Morfologi, cellbiologi, patologi  (svep)

Cellbiologi  (svep)

medicinsk cellbiologi  (uu)

Medical Cell Biology  (uu)

Indexterm och SAB-rubrik

Pancreatic β-cell

Store-operated

Calcium channels

Insulin secretion