2002 Fiscal Year Final Research Report Summary
Molecular Basis of Multiple Open States in Smooth Muscle Calcium Channels and Related Intracellular Signalling
| Project/Area Number |
13670041
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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 |
General physiology
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| Research Institution | Nagoya University |
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Principal Investigator |
NAKAYAMA Shinsuke Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (30192230)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Manabu Tohoku University Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (80302090)
ITO Yasushi Nagoya University, University Hospital, Research Associate University Hospital, Research Associate, 医学部附属病院, 助手 (80303650)
KUZUYA Masafumi Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10283441)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Calcium channels / Electrophysiology / Molecular basis / U-shaped inactivation / Slow deactivation / Multiple open states |
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| Research Abstract |
It is known that some smooth muscles possess both low- (LVA) and high voltage-activated (HVA) Ca^<2+> channel currents, and that the HVA current component is predominant in all smooth muscles. Previously, we have suggested that the conversion of the Ca^<2+> channel conformation from normal open (O1) to a second open state (O2) during large depoalrization is distinct from the long channel opening induced by Ca^<2+> channel agonists, and that these two mechanisms operate separately. As a result, a combination of DHP Ca^<2+> channel agonists and depolarization produces at least four open states in native smooth muscle Ca^<2+> channels.
During the tenure of the present research project entitled 'Molecular Basis of Multiple Open States in Smooth Muscle Calcium Channels and Related Intracellular Signalling', we have first examined whether the multiple open state model can systematically account for the characteristic features of 'U-shaped inactivation' and 'slow deactivation' in CHO cells exp
… More
ressing only smooth muscle _1 subunit of L-type Ca^<2+> channel (Ca,1.2b), using patch clamp techniques. The experiments have revealed that smooth muscle _1 subunit alone can reproduce 'U-shaped inactivation' and 'slow deactivation' properties, and also interaction of highly positive conditioning steps and Ca^<2+> agonists. The results imply that intramolecular structural changes and/or interactions in _1 subunit protein play the central roles. Furthermore, we have reconstructed the slow deactivation and U-shaped inactivation properties seen in cloned smooth muscle Ca^<2+> channels using computer calculation with multiple open state models. Taken Together, it is concluded that that the conformation of _1 subunit of L-type Ca2+ channel can be converted from O1 to O2 state in a voltage-dependent manner. This conversion is not predicted from the gating model described by Hodgkin & Huxley. We would like to propose that some modification in this basic model is presumably necessary to describe gating kinetics under more general conditions. Less
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