Calmodulin mediates calcium-dependent inactivation of the cerebellar type 1 inositol 1,4,5-trisphosphate receptor.
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.
Michikawa
T
T
Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Japan. takamich@ims.u-tokyo.ac.jp
Hirota
J
J
Kawano
S
S
Hiraoka
M
M
Yamada
M
M
Furuichi
T
T
Mikoshiba
K
K
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002147:Calmodulin / Q000502:physiology*; D002531:Cerebellum / Q000502:physiology*; D003593:Cytoplasm / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008051:Lipid Bilayers; D008081:Liposomes; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
D015220:Calcium Channels; D002147:Calmodulin; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008051:Lipid Bilayers; D008081:Liposomes; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C017967:W 7; D002118:Calcium