Regulation of Ca2+-release-activated Ca2+ current (Icrac) by ryanodine receptors in inositol 1,4,5-trisphosphate-receptor-deficient DT40 cells

K. Kiselyov, D. M. Shin, N. Shcheynikov, T. Kurosaki, S. Muallem

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)


Persistence of capacitative Ca2+ influx in inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)-deficient DT40 cells (DT40IP3R-/-) raises the question of whether gating of C2+-release activated Ca2+ current (Icrac) by conformational coupling to Ca2+-release channels is a general mechanism of gating of these channels. In the present work we examined the properties and mechanism of activation of Icrac Ca2+ current in wild-type and DT40IP3R-/- cells. In both cell types passive depletion of internal Ca2+ stores by infusion of EGTA activated a Ca2+ current with similar characteristics and time course. The current was highly Ca2+-selective and showed strong inward rectification, all typical of Icrac. The activator of ryanodine receptor (RyR), cADP-ribose (cADPR), facilitated activation of Icrac, and the inhibitors of the RyRs, 8-N-cADPR, ryanodine and Ruthenium Red, all inhibited Icrac activation in DT40IP3R-/- cells, even after complete depletion of intracellular Ca2+ stores by ionomycin. Wild-type and DT40IP3R-/- cells express RyR isoforms 1 and 3. RyR levels were adapted in DT40IP3R-/- cells to a lower RyR3/RyR1 ratio than in wild-type cells. These results suggest that IP3Rs and RyRs can efficiently gate Icrac in DT40 cells and explain the persistence of Icrac gating by internal stores in the absence of IP3Rs.

Original languageEnglish
Pages (from-to)17-22
Number of pages6
JournalBiochemical Journal
Issue number1
Publication statusPublished - 2001 Nov 15

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Regulation of Ca<sup>2+</sup>-release-activated Ca<sup>2+</sup> current (I<sub>crac</sub>) by ryanodine receptors in inositol 1,4,5-trisphosphate-receptor-deficient DT40 cells'. Together they form a unique fingerprint.

Cite this