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

K. Kiselyov, DongMin Shin, N. Shcheynikov, T. Kurosaki, S. Muallem

Research output: Contribution to journalArticle

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Abstract

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
Volume360
Issue number1
DOIs
Publication statusPublished - 2001 Nov 15

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Inositol 1,4,5-Trisphosphate Receptors
Ryanodine Receptor Calcium Release Channel
Cyclic ADP-Ribose
Chemical activation
Ruthenium Red
Ryanodine
Ionomycin
Inositol 1,4,5-Trisphosphate
Egtazic Acid
Protein Isoforms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Regulation of Ca2+-release-activated Ca2+ current (Icrac) by ryanodine receptors in inositol 1,4,5-trisphosphate-receptor-deficient DT40 cells",
abstract = "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.",
author = "K. Kiselyov and DongMin Shin and N. Shcheynikov and T. Kurosaki and S. Muallem",
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Regulation of Ca2+-release-activated Ca2+ current (Icrac) by ryanodine receptors in inositol 1,4,5-trisphosphate-receptor-deficient DT40 cells. / Kiselyov, K.; Shin, DongMin; Shcheynikov, N.; Kurosaki, T.; Muallem, S.

In: Biochemical Journal, Vol. 360, No. 1, 15.11.2001, p. 17-22.

Research output: Contribution to journalArticle

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AU - Kiselyov, K.

AU - Shin, DongMin

AU - Shcheynikov, N.

AU - Kurosaki, T.

AU - Muallem, S.

PY - 2001/11/15

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