2003 Fiscal Year Final Research Report Summary
Mechanisms of electrophysiological differentiation of cardiac cells during development
| Project/Area Number |
14570654
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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 | Nagoya University |
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Principal Investigator |
YASUI Kenji Nagoya University, Res. Inst. Of Environ. Med., Associate Professor, 環境医学研究所, 助教授 (70283471)
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| Co-Investigator(Kenkyū-buntansha) |
HORIBA Mitsuru Nagoya University, Res. Inst. Of Environ. Med., Assistant Professor, 環境医学研究所, 助手 (40345913)
LEE Jong-kook Nagoya University, Res. Inst. Of Environ. Med., Assistant Professor, 環境医学研究所, 助手 (60303608)
KODAMA Itsuo Nagoya University, Res. Inst. Of Environ. Med., Professor, 環境医学研究所, 教授 (30124720)
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| Project Period (FY) |
2002 – 2003
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| Keywords | development / heart / mouse / T-type / L-type / calcium / mRNA / current |
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| Research Abstract |
Mouse embryonic heart initiates to beat at 8.5 dpc (days post coitum) and its spontaneous activity become regular at 9.5 dpc, when the heart shape is tube-like. Cardiac ventricle isolated from embryonic heart at 9.5 dpc beats spontaneously. With development, ventricle loses its pacing activity. We investigate the developmental changes of Ca^<2+> channel in mouse cardiac ventricle (9.5 dpc, 18 dpc and adult) using whole-cell patch clamp and a real-time PCR.
1)T-type Ca^<2+> during development
Two subtypes (Ca_v3.1 and Ca_v3.2) have been cloned for α_1 subunit of the T-type Ca^<2+> in cardiac muscle. Large T-type Ca^<2+> (I_<Ca, T>) was observed at both 9.5 dpc and 18 dpc, displaying similar voltage-dependence and kinetics of activation and inactivation. The current was inhibited by Ni^<2+> relatively low concentrations (IC_<50> 26-31 μM). I_<Ca, T> was undetectable in adult myocytes. PCR analysis revealed that Ca_v3.2 (α_<IH>) mRNA is the predominant subtype encoding T-type Ca^<2+> at cha
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nnels both E9.5 and E18. Ca_v3.1 (α_<IG>) mRNA increased from E9.5 to E18, but remained low compared with Ca_v3.2 mRNA during the whole embryonic period. In the adulthood, in contrast, Ca_v3.1 mRNA is greater than Ca_v3.2 mRNA. These results indicate that Ca_v3.2 underlies the functional T-type Ca^<2+> channels in the embryonic murine heart, and there is a subtype switching of transcripts from Ca_v3.2 to Ca_v3.1 in the perinatal period.
2)L-type Ca^<2+> during development
L-type Ca^<2+> are coded by four distinct genes (Ca_v1.1,Ca_v1.2,Ca_v1.3 and Ca_v1.4). Ca_v1.2 and Ca_v1.3 channels are expressed in the adult heart. Ca_v1.2 Ca^<2+> is the major L-type Ca^<2+> in cardiac muscle. Ca_v1.3 Ca^<2+> functions cardiac pacing in sinoatrial node. Activation and inactivation curve of I_<Ca-L> in cardiac ventricle at 9.5 was shifted more negative potential than 18 dpc and adult. Ca_v1.3 mRNA was expressed at 9.5 dpc, but down-regulates in the second half of embryonic development. Cal_v1.2 mRNA expression increased through all developmental stages (9.5 dpc,18 dpc and adult). We are also analyzing alternative splicing of Ca_v1.3. Less
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