Ca2+ modulation of Ca2+ release-activated Ca2+ channels is responsible for the inactivation of its monovalent cation current.
The Ca(2+) release-activated Ca(2+) (CRAC) channel is the most well documented of the store-operated ion channels that are widely expressed and are involved in many important biological processes. However, the regulation of the CRAC channel by intracellular or extracellular messengers as well as its molecular identity is largely unknown. Specifically, in the absence of extracellular divalent cations it becomes permeable to monovalent cations with a larger conductance, however this monovalent cation current inactivates rapidly by an unknown mechanism. Here we found that Ca(2+) dissociation from a site on the extracellular side of the CRAC channel is responsible for the inactivation of its Na(+) current, and Ca(2+) occupancy of this site otherwise potentiates its Ca(2+) as well as Na(+) currents. This Ca(2+)-dependent potentiation is required for the normal functioning of CRAC channels.
Su
Zhengchang
Z
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
Shoemaker
Richard L
RL
Marchase
Richard B
RB
Blalock
J Edwin
JE
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D015640:Ion Channel Gating; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism*; D008670:Metals / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism*
D015220:Calcium Channels; D008670:Metals; D012964:Sodium; D002118:Calcium