Abstract
The dependency of purified mouse cerebellar type 1 inositol 1,4,5-trisphosphate receptor (IP3R1)/Ca2+ channel function on cytoplasmic Ca2+ was examined. In contrast to the channels in crude systems, the purified IP3R1 reconstituted into planar lipid bilayers did not show the bell-shaped dependence on Ca2+. It was activated with increasing Ca2+ sublinearly without inhibition even up to 200 microM. The addition of calmodulin to the cytoplasmic side inhibited the channel at high Ca2+ concentrations. Calmodulin antagonists reversed the Ca2+-dependent inactivation of the native channels in cerebellar microsomes. These results indicate that the bell-shaped dependence on cytoplasmic Ca2+ is not an intrinsic property of the IP3R1, and the Ca2+-dependent inactivation is directly mediated by calmodulin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / physiology*
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Calcium Channels / chemistry
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Calcium Channels / physiology*
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Calcium Signaling / physiology
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Calmodulin / physiology*
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Cerebellum / physiology*
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Cytoplasm / physiology
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Enzyme Inhibitors / pharmacology
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Inositol 1,4,5-Trisphosphate Receptors
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Lipid Bilayers
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Liposomes
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Membrane Potentials / physiology
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Mice
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Microsomes / drug effects
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Microsomes / metabolism
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Patch-Clamp Techniques
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Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / physiology*
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Sulfonamides / pharmacology
Substances
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Calcium Channels
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Calmodulin
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Enzyme Inhibitors
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Inositol 1,4,5-Trisphosphate Receptors
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Lipid Bilayers
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Liposomes
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Receptors, Cytoplasmic and Nuclear
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Sulfonamides
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W 7
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Calcium