A role for Ca2+-sensitive nonselective cation channels in regulating the membrane potential of pancreatic beta-cells
A role for Ca2+-sensitive nonselective cation channels in regulating the membrane potential of pancreatic beta-cells. C A Leech and J F Habener Laboratory of Molecular Endocrinology, Howard Hughes Medical Institute, Harvard Medical School, Massachusetts General Hospital, Boston 02114-2696, USA. leec...
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Published in | Diabetes (New York, N.Y.) Vol. 47; no. 7; pp. 1066 - 1073 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.07.1998
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Subjects | |
Online Access | Get full text |
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Summary: | A role for Ca2+-sensitive nonselective cation channels in regulating the membrane potential of pancreatic beta-cells.
C A Leech and
J F Habener
Laboratory of Molecular Endocrinology, Howard Hughes Medical Institute, Harvard Medical School, Massachusetts General Hospital,
Boston 02114-2696, USA. leech@helix.mgh.harvard.edu
Abstract
The incretin hormones, glucagon-like peptide 1 and pituitary adenylyl cyclase-activating polypeptide, are proposed to activate
a maitotoxin (MTX)-sensitive, Ca2+-dependent nonselective cation current in pancreatic beta-cells and insulinoma cells. This
MTX-sensitive current is present in human beta-cells as well as in mouse and rat beta-cells, and is accompanied by a rise
in cytosolic Ca2+ in voltage-clamped cells in which the activation of voltage-dependent Ca2+ channels is prevented. Activation
of the nonselective cation current is inhibited by reduction of disulfide bonds with intracellular, but not extracellular,
dithiothreitol, and is also abolished by intracellular dialysis with trypsin. The nonselective cation channels that carry
this current have a conductance of about 30 pS, with Na+ as the major extracellular cation. We estimate that these cation
channels are expressed on beta-cells at a density similar to that of ATP-sensitive potassium channels (K(ATP) channels) and
exhibit spontaneous activity at basal glucose concentrations. We propose that this spontaneous cation channel activity constitutes
at least part of the depolarizing background conductance that permits changes in the activity of K(ATP) channels to regulate
the resting potential of beta-cells. |
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ISSN: | 0012-1797 1939-327X |
DOI: | 10.2337/diabetes.47.7.1066 |