1998 Fiscal Year Final Research Report Summary
Molecular Mechanisms for Regulation of Renal Ion Channels
| Project/Area Number |
09670059
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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 | Iwate Medical University (1998)
Osaka Medical College (1997) |
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Principal Investigator |
KUBOKAWA Manabu Physiology II,Iwate Medical University Prof., 歯学部, 教授 (70153327)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Yoshiaki Physiology, Osaka Medical College Assist.Prof., 医学部, 講師 (70268192)
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| Project Period (FY) |
1997 – 1998
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| Keywords | kidney / proximal tubule / ion transport / K^+ channel / protein kinase A / protein kinase C / cyclic GMP / phosphorylation |
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| Research Abstract |
The regulatory mechanism and physiological significance of K^+ channels in the basolateral membrane of proximal tubule cells have been investigated by using the patch-clamp technique. In bullfrog kidneys, inwardly rectifying K^+ channels with the inward conductance of about 50 pS are present in the basolateral membrane of isolated proximal tubule tubule cells. Activity of the K^+ channel is enhanced by intracellular alkalinization, and is inhibited by its acidification in cell-attached patches in the presence of H^+ ionophore, FCCP.The channel is regulated also by intracellular ATP, and plays a major role in formation of the basolateral membrane potential of the proximal tubule cell.
In opossum kidney proximal tubule (OKP) cells, the K^+ channel with inward conductance of about 90 pS was observed, which was also reported to be pH-sensitive and regulated by ATP.Activity of the K^+ channel is inhibited by protein kinase inhibitors, and is enhanced by application of dibutyryl-cAMP or dibutyryl-cGMiP in cell-attached patches. Direct application of cAMP- or cGMP-dependent protein kinase (PKA or PKG) enhanced channel activity in inside-out patches in the presence of ATP (3 mM). In contrast, activity of the K^+ channel is inhibited by direct application of protein kinase C (PKC) in the presence of Ca^<2+> (1muM).These results suggest that the K^+ channel in OKP cells is regulated at least in part by two different phosphorylation processes, PKA or PKG-mediated phosphorylation and PKC-mediated phosphorylation. Moreover, our results suggest that atrial natriuretic peptide is one of the agonist which stimulates PKG-mediated phosphorylation in OKP cells.
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[Publications] Kubokawa, M., Nakaya, S., Yoshioka Y., Nakamura, K., Sato, F., Mori, Y., and Kubota, T.: "Activation of inwardly recitifying K^+ channel in OK proximal tubule cells by cGMP-dependent phosphorylation process." Jpn.J.Physiol.48. 467-476 (1998)
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