A GTP-dependent step in the activation mechanism of capacitative calcium influx.
Calcium influx in electrically non-excitable cells is regulated by the filling state of intracellular calcium stores. Depletion of stores activates plasma membrane channels that are voltage-independent and highly selective for Ca2+ ions. We report here that the activation of plasma membrane Ca2+ currents induced by depletion of Ca2+ stores requires a diffusible cytosolic factor that washes out with time when dialyzing cells in the whole-cell configuration of the patch-clamp technique. The activation of calcium release-activated calcium current (ICRAC) by ionomycin- or inositol 1,4,5-trisphosphate-induced store depletion is blocked by guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) and guanyl-5'-yl imidodiphosphate, non-hydrolyzable analogs of GTP, suggesting the involvement of a GTP-binding protein. The inhibition by GTP gamma S occurs at a step prior to the activation of ICRAC and is prevented by the addition of GTP. We conclude that the activation mechanism of depletion-induced Ca2+ influx encompasses a GTP-dependent step, possibly involving an as yet unidentified small GTP-binding protein.
Fasolato
C
C
Department of Membrane Biophysics, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Federal Republic of Germany.
Hoth
M
M
Penner
R
R
D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives; D005459:Fluorides / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism*; D007202:Indicators and Reagents; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D015640:Ion Channel Gating; D015759:Ionomycin / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured
D017607:Aluminum Compounds; D015220:Calcium Channels; D007202:Indicators and Reagents; D004533:Egtazic Acid; D015759:Ionomycin; D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D005459:Fluorides; D002118:Calcium; C032311:aluminum fluoride