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1D Ca2+ channel) in insulin secreting cells
1 Pharmacology, Tulane University, New Orleans, LA, USA
2 Pharmacology, Yale University, New Haven, CT, USA
3 Pharmacology, Medical College of Virginia, Richmond, VA, USA
* To whom correspondence should be addressed. E-mail: mli{at}tulane.edu.
Chronic exposure of pancreatic 
-cells to high concentrations of glucose impairs the insulin secretory response to further glucose stimulation. This phenomenon is referred to as glucose desensitization. It has been shown that glucose desensitization is associated with abnormal elevation of -cell basal intracellular free Ca2+ concentration. We have investigated the relationship between the basal intracellular free Ca2+ and the L-type (Cav1.3) Ca2+ channel translocation in insulin secreting cells. Glucose stimulation or membrane depolarization induced a nifedipine-sensitive Ca2+ influx, which was attenuated when the basal intracellular Ca2+ concentration was elevated. Using voltage-clamp techniques, we found that changing intracellular Ca2+ concentration could regulate the amplitude of the Ca2+ current. This effect was attenuated by drugs that interfere with the cytoskeleton. Immunofluorescent labeling of Cav1.3 showed an increase in the cytoplasmic distribution of the channels under high [Ca2+]i conditions by deconvolution microscopy. In addition to their plasma membrane expression, the Cav1.3 channels were also detected in the cytoplasm by deconvolution immunofluorescent microscopy. The intracellular Ca2+ concentration-dependent translocation of Cav1.3 channel was also demonstrated by Western blot analysis of biotinylation/NeutrAvidin-bead-eluted surface proteins in cells pre-incubated at various intracellular Ca2+ concentrations. These results suggest that Cav1.3 channel trafficking is involved in glucose desensitization of pancreatic -cells.
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