A store-operated nonselective cation channel in human lymphocytes.
1. Agonist interaction with phospholipase C-linked receptors at the plasma membrane can elicit both Ca2+ and Na+ influxes in lymphocytes. While Ca2+ influx is mediated by Ca2+ release-activated Ca2+ (CRAC) channels, the pathway responsible for Na+ influx is largely unknown. 2. We show that thapsigargin, ionomycin, ADP-ribose and IP3 activated a nonselective cation channel in lymphocytes that had a slightly outwardly rectifying I-V relationship, and a single channel conductance of 23.1 pS. We termed this channel a Ca2+ release-activated nonselective cation (CRANC) channel. 3. On activation in cell-attached configuration, switching to an inside-out configuration abolished CRANC channel activity. 4. Transfection of Jurkat T cells with antisense oligonucleotides for LTRPC2 reduced capacitative Ca2+ entry. 5. These results suggest that CRANC channels are responsible for the Na+ influx as well as a portion of the Ca2+ influx in lymphocytes induced by store depletion, that sustained activation of CRANC channels requires some property of the environment of a cell depleted of its Ca2+ stores; and that LTRPC2 protein is a likely component of the CRANC channel.
Su
Zhengchang
Z
Department of Physiology and Biophysics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, 1918 University Boulevard, Birmingham, Alabama 35294, USA.
Guo
Xiaochuan
X
Barker
Douglas S
DS
Shoemaker
Richard L
RL
Marchase
Richard B
RB
Blalock
J Edwin
JE
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism*; D019169:Jurkat Cells; D015471:Leukemia, Basophilic, Acute; D008214:Lymphocytes / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism; D050053:TRPM Cation Channels; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection
D002412:Cations; D004791:Enzyme Inhibitors; D007473:Ion Channels; D008565:Membrane Proteins; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D019284:Thapsigargin; D012964:Sodium; D002118:Calcium