1997 Fiscal Year Final Research Report Summary
Molecular Diversity of K Channels in Cardiovascular System.
| Project/Area Number |
08044313
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Biological pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
WATANABE Minoru Nagoya City University, Chemical Pharmacology, Professor, 薬学部, 教授 (50012638)
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| Co-Investigator(Kenkyū-buntansha) |
WALSH Michae カルガリー大学, 医学部, 教授
GILES Wayne カルガリー大学, 医学部, 教授
OHYA Susumu Nagoya City University, Chemical Phamacology, Junior Lecturer, 薬学部, 助手 (70275147)
MURAKI Katsuhiko Naogya City University, Chemical Pharmacology, Assistant Professor, 薬学部, 講師 (20254310)
IMAIZUMI Yuji Nagoya City University, Pharmacology and Therapeutics, Professor, 薬学部, 教授 (60117794)
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| Project Period (FY) |
1996 – 1997
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| Keywords | A-type K current / smooth muscle / RT-PCR technique / Kv4.3 / HEK 293 cell / arachidonic acid / Ca^<2+>-dependent K^+ channel / voltage-dependent Ca^<2+> channel |
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| Research Abstract |
Early inactivating K^+ (A type) current can be recorded widely in neuron, cardiac myocytes and smooth muscle cells. the current plays significant roles for the regulation of action potential firing and formation of the repolarizing phase of an action potential. Although several distinct genes encoding the K^+ channels responsible for A type K^+ current (I_A) in cardiac myocytes and brain have been reported, nothing is known in smooth muscle cells. The electrophysiological characteristics of I_A in smooth muscle cells (vas deferens, colon and ureter) and similar to those in cardiac myocytes. Nevertheless, it was found that arachidonic acid selectively blocks the I_A in smooth muscle cells (Am.J.Physiol.1997). The possibility that the K^+ channel gene for I_A in smooth muscle is deferent from that in cardiac myocytes was examined using RT-PCR techniques. In addition, the related K^+ channels in smooth muscle cells in the rat was cloned. Kv1.4,4.2 and 4.3 have been reported as K^+ channel
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genes in brain and cardiac myocytes. Based on the expression levels of mRNAs of these genes, it was found taht Kv4.3 is predominant among them in smooth muscle cells. Moreover, Kv4.3 in smooth muscle cells was a new spliced variant of the original Kv4.3 (Kv.4.3M) in brain and has additional 19 amino acids in cytosolic domain close to the C terminus (Kv4.3L) (FEBS Letters, 1997). In the rat heart, the mRNA level of Kv4.3L was higher than that of Kv4.3M.Electrophysiological characteristics of Kv1.4,4.2,4.3M and 4.3L K^+ channels were determined in HEK 293 cells in which one of these channel types was highly expressed. The voltage-dependence of activation and inactivation, the recovery time course from inactivation and the sensitivity to arachidonic acid of Kv4.3L were not significantly different from those of Kv4.3M.Further research is required to elucidate the functional roles of additional 19 amino acids in Kv4.3L.It was also found that the different expression levels of mRNAs encoding the large conductance Ca^<2+> -dependent K^+ channels and the voltage-dependent Ca^<2+> channels in various type of smooth muscle cells, at least in part, explains the difference in membrane excitability in different types of smooth muscle cells. Less
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