Requirement of the inositol trisphosphate receptor for activation of store-operated Ca2+ channels.
The coupling mechanism between endoplasmic reticulum (ER) calcium ion (Ca2+) stores and plasma membrane (PM) store-operated channels (SOCs) is crucial to Ca2+ signaling but has eluded detection. SOCs may be functionally related to the TRP family of receptor-operated channels. Direct comparison of endogenous SOCs with stably expressed TRP3 channels in human embryonic kidney (HEK293) cells revealed that TRP3 channels differ in being store independent. However, condensed cortical F-actin prevented activation of both SOC and TRP3 channels, which suggests that ER-PM interactions underlie coupling of both channels. A cell-permeant inhibitor of inositol trisphosphate receptor (InsP3R) function, 2-aminoethoxydiphenyl borate, prevented both receptor-induced TRP3 activation and store-induced SOC activation. It is concluded that InsP3Rs mediate both SOC and TRP channel opening and that the InsP3R is essential for maintaining coupling between store emptying and physiological activation of SOCs.
Ma
H T
HT
Department of Biochemistry and Molecular Biology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
Patterson
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RL
van Rossum
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DB
Birnbaumer
L
L
Mikoshiba
K
K
Gill
D L
DL
D000199:Actins / Q000378:metabolism; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015759:Ionomycin / Q000494:pharmacology; D047028:Macrocyclic Compounds; D008387:Marine Toxins; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D013324:Strontium / Q000378:metabolism; D050052:TRPC Cation Channels; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D000199:Actins; D001896:Boron Compounds; D015220:Calcium Channels; D004075:Diglycerides; D004791:Enzyme Inhibitors; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D008387:Marine Toxins; D010080:Oxazoles; D018160:Receptors, Cytoplasmic and Nuclear; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C096351:transient receptor potential cation channel, subfamily C, member 1; C108644:xestospongin A; D015759:Ionomycin; D019284:Thapsigargin; C059041:calyculin A; D002217:Carbachol; C109986:2-aminoethoxydiphenyl borate; D010749:Phosphoprotein Phosphatases; D010738:Type C Phospholipases; D002118:Calcium; D013324:Strontium