TY - JOUR
T1 - Requirement of the inositol trisphosphate receptor for activation of store-operated Ca2+ channels
AU - Ma, Hong Tao
AU - Patterson, Randen L.
AU - Van Rossum, Damian B.
AU - Birnbaumer, Lutz
AU - Mikoshiba, Katsuhiko
AU - Gill, Donald L.
PY - 2000/3/3
Y1 - 2000/3/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034009899&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034009899&partnerID=8YFLogxK
U2 - 10.1126/science.287.5458.1647
DO - 10.1126/science.287.5458.1647
M3 - Article
C2 - 10698739
AN - SCOPUS:0034009899
SN - 0036-8075
VL - 287
SP - 1647
EP - 1651
JO - Science
JF - Science
IS - 5458
ER -