Molecular analysis and sensitivity to arachidonic acid of voltage-dependent KィイD1+ィエD1 channel, Kv4.3

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10672049
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: NAGOYA CITY UNIVERSITY
• Principal Investigator: MAIZUMI Yuji NAGOYA CITY UNIVERSITY, PHARMACOLOGY & THERAPEUTICS, PROFESSOR, 薬学部, 教授 (60117794)
• Co-Investigator(Kenkyū-buntansha): OHYA Susumu NAGOYA CITY UNIVERSITY, PHARMACOLOGY & THERAPEUTICS, JUNIOR LECTURER, 薬学部, 助手 (70275147)
• Project Period (FY): 1998 – 1999
• Keywords: Kv4.3 / in situ hybridization / RT-PCR / C-terminal mutagenesis / HEK293 cells / rate of recovery / hippocampus

Research Abstract

In situ hybridization and RT-PCR analyses has revealed that, among three Kv4.3 splice variants (a, b, and c) with distinct C-terminal cytoplasmic domains, the mRNA for Kv4.3a is abundant in cerebral cortex, cerebellum, olfactory bulb, and medulla oblongata, whereas the mRNA of Kv4.3c is localized mainly to hippocampus. Three new distinct splice variants of Kv4.3 (Kv4.3d, e and f), which consist of 601, 635, and 628 amino acids, respectively, and have divergent C-terminal cytoplasmic domains, were isolated from rat brain by RT-PCR. Kv4.3b, d, e and f are expressed at much lower levels in brain. Mutagenesis which removed 149 amino acids in C-terminal domain of Kv4.3a significantly slowed its rate of recovery from inactivation as measured in heterologous expression in HEK293 cells. Surprisingly, however, neither the rate of inactivation nor voltage dependence of the activation and inactivation were changed.