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2001 Fiscal Year Final Research Report Summary

Role of FKBP in the interaction between ryanodine raeptor/Ca^2 release channel and volatile anesthetics

Research Project

Project/Area Number 12670090
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

ONOUE Hitoshi  Graduate School of Medical Sciences, KYUSHU UNIVERSITY, Assistant Prof., 大学院・医学研究院・生体情報薬理, 講師 (70221166)

Project Period (FY) 2000 – 2001
KeywordsCa^<2+> / ryanodine receotor / FKBP / volatile anesthetics / interaction / SR
Research Abstract

1. Effects of halothane on [^3H]ryanodine binding to native and FKBP-depleted skeletal muscle SR (SkSR) fraction [^3H]ryanodine binding study was performed against rabbit native and FKBP-depleted SkSR at various concentrations (10 nM-1 mM) of free Ca^<2+>. At all [Ca^<2+>]_<free>, [^3H]ryanodine binding were significantly (2-2.5 fold) higher in FKBP depleted SkSR compared to native SR. Addition of halothane slightly (up to 20 %) enhanced the [^3H]ryanodine binding to native SkSR throughout the [Ca^<2+>]_<free> examined. This was also observed in FKBP-depleted SkSR except at the [Ca^<2+>]_<free> of 100 nM, which is close to physiological [Ca^<2+>]_<free>, the [^3H]ryanodine binding was enhanced by 70 % Ryanodine binds to open RYR, thus our results suggest that removal of FKBP12 from RYR1 significantly increases the number of channels open upon stimulation by halothane at physiological [Ca^<2+>]_<free>.
2. Effects of halothane on Ca^<2+> loading and release of native and FKBP-depleted SkS … More R-ATP-energized Ca^<2+> loading of rabbit native and FKBP-depleted SkSR was initiated by adding ATP and Ca^<2+> into SR suspension. Ca^<2+> loading rate of FKBP-depleted SkSR was somehow slower compared to native SR. When halothane was added after the [Ca^<2+>] run down to baseline, Ca^<2+> release from the SR vesicles was observed. In native SkSR, [Ca^<2+>] ran down to baseline. In FKBP-depleted SkSR, in contrast, run down of [Ca^<2+>] was little and reached a plateau which was significantly higher than the baseline level. When ruthenium red, a drug that locks the RYR at the closed state, was added at the plateau phase, [Ca^<2+>] restarted running down and reached the baseline level. These results suggested that depletion of FKBP12 makes RYR1 more sensitive to halothane and the channel activation by the drug is prolonged.
3. Interaction of RYR2 of species other than dog with FKBP12-It has been reported that not only FKBP12.6 but also FKBP12 binds to cardiac SR (CSR) from various species other than dog including rat, mouse and rabbit, thus RYR2 in those animals are expected to bind FKBP12. We examined by co-immunoprecipitation and pull down assay of (His)_6FKBP12, whether FKBP12 bound to the CSR is tightly associated with RYR2. FKBP12 as well as FKBP12.6 bound to FKBP CSR of rat, mouse and rabbit. However, FKBP12 was not associated with RYR2 immunoprecipitated from FKBP12-bound CSR even after CSR was incubated with high (10 μM) of FKBP12. Vice versa, RYR2 was neither co-immunoprecipitated with FKBP12 nor co-purified with (His)_6FKBP12 by Ni-NTA. Our results suggested FKBP12 binds to CSR but does not tightly associate with RYR2. FKBP12 might bind not to RYR2 but other component of CSR membrane, or the interaction of FKBP12 with RYR2 is with rapid on-off rate. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Onoue H.: "Interaction of immunophilin FKBP and intracellular Ca^<2+> release channels"Fukuoka Igaku Zasshi. 92(7). 272-277 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Doira N.: "Reconstitution in lipid bilayer of smooth muscle cation channels activated through a GTP-binding protein"J. Smooth Muscle Res.. 37(2). 39-51 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inoue R.: "The transient receptor potentiol protein homologue TRP6 is the essential component of vascular α_1-adrenoceptor-activated Ca^<2+>-permeable cation channel"Circ. Res.. 88(3). 325-332 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Bauer V.: "Effects of superoxide generating systems on muscle tone, cholinergic and NANC responses in cat airway"J. Auton. Nerv. Syst.. 79(1). 34-44 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Onoue H.: "Heterooligomer of type 1 and type 2 inositol 1, 4, 5-trisphosphate receptor expressed in rat liver membrane fraction exists as tetrameric complex"Biochem. Biophys. Res. Commun.. 267(3). 928-933 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito Y.: "The prostaglandin E series modulates high-voltage-activated calcium channels probably through the EP3 receptor in rat paratracheal ganglia"Neuropharmacology. 39-2. 181-190 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Onoe H., Itonaga Y., Ito Y.: "Interaction of iimunophilin FKIP and intracellular Ca^<2+> release channels"Fukuoka Igaku Zasshi. 92 (7). 272-277 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Doira N., Hanano T., Onoue H., Nakano H., Ito Y., Inoue R.: "Reconstitution in lipid bilayer of smooth muscle cation channels activated through a GTP-binding protein"J. Smooth Muscle Res.. 37 (2). 39-51 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoue R., Okada T., Onoue E., Hara Y., Shimizu S., Naitoh S., Ito Y., Mori Y.: "The transient receptor potential protein homologue TRP6 is the essential component of vascularα_1-adrenoceptor-activated Ca^<2+>-permeable cation channel"Circ. Res.. 88. 325-332 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Bauer, V., Nakajima, T., Pucovsky, V., Onoue, H., Ito, Y.: "Effects of superoxide generating systems on muscle tone, cholinergic and NANC responses in cat airway"J. Auton. Nerv. Syst.. 79(1). 34-44 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Onoue, H., Tanaka E., Tanaka, K., Doira, R, Ito, Y.: "Heterooligomer of type 1 and type 2 inositol 1, 4, 5-trisphosphate receptor expressed in rat liver membrane fraction exists as tetrameric complex"Biochem. Biophys. Res. Comnn.. 267 (3). 928-933 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito, Y., Murai, Y., Ishibashi, E., Oncue, E., Akaike, N.: "The prostaglandin E series modulates high-voltage-activated calcium channels probably through the EP3 receptor in rat paratracheal ganglia"Neuropharmacology. 39 (2). 181-190 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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