1999 Fiscal Year Final Research Report Summary
Regulation mechanism of cardiac L-type CaィイD12+ィエD1 channel by nitric oxide
| Project/Area Number |
10670676
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Teikyo University |
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Principal Investigator |
FURUKAWA Taiji Teikyo University, Medicine, Research associate, 医学部, 助手 (70276731)
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| Co-Investigator(Kenkyū-buntansha) |
NUKADA Toshihide Tokyo Institute of Psychiatory, Neurochemistry, Associate Professor, 東京都精神医学総合研究所・神経化学部門, 副参事 (80189349)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Nitric oxide / Ca channel / Xenopus oocyte / gene expression / protein kinase A / signal transduction / second messenger / protein kinase G |
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| Research Abstract |
In order to elucidate sub-cellular mechanism in regulation of L-type cardiac CaィイD12+ィエD1 channel by β-adrenergc stimulation and PKA activation, we cloned PKA anchoring protein (AKAP) and expressed the protein in Xenopus oocyte expression system. The CaィイD12+ィエD1 channel activities were measured electrophysiologically as membrane BaィイD12+ィエD1 current. The oocytes expressed with CaィイD12+ィエD1 channel αィイD21cィエD2, αィイD22ィエD2, βィイD21aィエD2, GィイD2SィエD2α and βィイD22ィエD2 adrenergic receptor did not show the augmentation of CaィイD12+ィエD1 channel by stimulation with isoproterenol (ISO). ISO stimulated the channel when clude bovine poly(A)+RNA was introduced into the oocyte. Cloned AKAP-79, AKAP-15 and calmodulin failed to reconstruct the Ca channel stimulation by ISO. Furthermore, ISO reduced the Ca channel activity with AKAP-79 expression. The reduction was dependent on the amount of AKAP-79 cRNA injection. The BaィイD12+ィエD1 current amplitude also reduced upon expression of AKAP-79. These data suggest that CaィイD12+ィエD1 channel stimulation through β-adrenergic stimulation requires intra-cellular protein(s) other than PKA anchoring proteins or calmodulins. These results were presented in 71 th scientific meeting of american heart association (1998, Dallas).
Meanwhile, using the same Xenopus oocyte expression system, we succeeded to assess the blocking potencies of several CaィイD12+ィエD1 channel antagonists on multiple subtypes of expressed Ca channel. The results were published in J Pharmacol Exp Ther as achievement of this grant.
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[Publications] Furukawa T, Maruyama Y, Koyama Y, Hangai K, Nakamura Y, Midera T, Yamakawa T, Endo G, Yamanaka M: "Subtype selectivity of series of dihydropyridine Ca(2+) antagonists on cloned Ca(2+) channels"XIII World Congress of Cardiology (Proceedings), Editore, Rio de Janeiro, Brazil. 193-196 (1998)
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