Mechanisms of ion channel localization during synapse formation
| Project/Area Number |
15500265
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurochemistry/Neuropharmacology
|
|---|
| Research Institution | Saitama Medical School |
|---|
Principal Investigator |
NAKAHIRA Kensuke Saitama Medical School, Department of Physiology, lecturer, 医学部, 講師 (10260043)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | Kv4.2 / Voltage-dependent K^+ channel / synapse / localization / mossy fiber / cerebellar granule cells |
|---|
| Research Abstract |
Subcellular localization of ion channels is important for compartmentalized neuronal function. We found that localization of Kv4.2, an A-type voltage-gated K^+ channel, changes from soma to the dendrites and synapses during synaptogenesis, and the neuronal activity plays a key role in this change. Stimulation with glutamate, NMDA or AMPA also induces dendritic localization of Kv4.2 without formation of synapses in vitro. This effect of glutamate, NMDA and AMPA were abolished by chelating external or internal Ca^<2+>, but not by an application of nifedipine, indicating the signaling pathway are dependent on Ca^<2+> influx through glutamate receptors. The effect of NMDA was abolished by CaMKII inhibitor, KN62. Inhibition of kinases, MEK, calcineurin or PI3-kinase, showed no effect on AMPA stimulation. Activation of PKA or PKC induced Kv4.2 localization similar to that by glutamate, however, inhibition of PKA or PKC did not inhibit the effect of glutamate. These data indicated that the regulation of localization of Kv4.2 by glutamate was carried out by complex, multiple signaling pathways. Inhibition by cycloheximide indicated the requirement of newly formed proteins. Further investigation is necessary to elucidate which protein, newly formed Kv4.2 or some regulator proteins, is essential. GFP-Kv4.2 fusion proteins including N-terminal and C-terminal fusions failed to show specific localization by glutamate stimulation. This suggested the steric effect of GFP tag interrupted protein- protein interaction.
|
Report
(3 results)
Research Products
(3 results)
