1996 Fiscal Year Final Research Report Summary
Study on regulatory mechanisms of gap junction conductance of cardiac muscle
| Project/Area Number |
07670070
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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 | Fukuoka University |
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Principal Investigator |
IMANAGA Issei Fukuoka Univ., School of Medicine, Professor, 医学部, 教授 (40078613)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Masumi Fukuoka Univ., School of Medicine, Asst.Prof., 医学部, 助教授 (40223276)
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| Project Period (FY) |
1995 – 1996
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| Keywords | cardiac muscle / gap junction / gap juntion conductance / hypoxia / c-AMP / PKA inhibiotr / Ca-overload / acidosis |
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| Research Abstract |
Purpose : The cardiac gap junction which is composed of channels is playing main role in cell-to-cell electrical coupling, It is generally indicated that the gap junction channels are closed by Ca^<2+> and H^+, and opened by c-AMP.It has been observed that arrhythmias due to conduction disturbances are often brought about and intracellular Ca^<2+> and H^+ ions are increased in hypoxia. In this study, infuences of hypoxia, intrabcellular Ca-overload and intracellular acidosis on gap junction electrical (longitudinal internal resistance) (ri) and conduction velocity (CV), and effectsd of c-AMP on them were examined. Results 1)By the three-compartments-chamber with shunt resistance circuit, ri and CV could simultaneously be measured on isolated multicellular cardiac tissue. 2)Time dependent increase in ri consisted with the decrease in CV induced by hypoxia. 3)c-AMP prevented and retored the deteriorated alterations of ri and CV induced by hypoxia, while it accelerated the reduction of Vmax of transmembrane action potential. 4)Increase in ri and decrease in CV induced by intracellular Ca^<2+>-overload were mitigated by lower dosis of c-AMP.5)Increse in ri and decrease in CV induced by intracellular acidosis were mitigated by c-AMP, when pH was more than 6.5.6)These effects of c-AMP were abolished by PKA inhibitor. 7)Alterations of ri and CV and effects od c-AMP on them were evidenced by morphological findings. Conclusions : It is suggested that electrical cell-to-cell uncoupling in hypoxia is due to closing effects of Ca^<2+> and H^+ ions on the gap junction channels, and c-AMP-PKA opens the closed channels or acts on the channels as up-regulation by phosphorylation of the connexin. Whether binding potency of Ca^<2+> and H^+ ions to the connexin is modified by phosphorylated state of the connexin is proposed as a novel problem.
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