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[Abstract Title]. - Society for Neuroscience

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Program#/Poster#: 234.4/C28<br />

Topic: B.04.c. Potassium channels: Physiology<br />

Support: Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and<br />

Technology of Japan<br />

Keio Gijuku Academic Development Funds<br />

Kanehara Foundation Research Grant<br />

<strong>Title</strong>: Regulation of Kv4.2 by neuronal activity<br />

Authors: *M. NURIYA, T. ITO, M. YASUI;<br />

Pharmacol, Keio Univ., Shinjuku, Japan<br />

<strong>Abstract</strong>: Voltage gated ion channels are crucial to neuronal functions both in physiological and<br />

pathological conditions. Kv4.2 constitutes a major component of A-type potassium current and is<br />

localized specifically at dendrites and soma, where it plays critical roles in propagations of<br />

voltage in<strong>for</strong>mation by regulating the excitability of dendrites. While functional modifications of<br />

Kv4.2 by its phosphorylations through several signal transduction pathways have been described,<br />

physiological stimuli that modify these phosphorylation states remain mostly unknown. Here, we<br />

report that neuronal activity induces rapid and specific dephosphorylation of Kv4.2 in primary<br />

cultured cortical neurons. Activation of N-methyl-D-aspartic acid (NMDA) receptor but not αamino-3-hydroxy-5-methylisoxazole-4-propionic<br />

acid (AMPA) receptor is necessary and<br />

sufficient <strong>for</strong> this dephosphorylation. As bulk calcium influx by ionomycin does not mimic this<br />

NMDA receptor activation effect, some specific signal transductions other than a mere rise of<br />

cytoplasmic calcium concentration appear to be responsible <strong>for</strong> this rapid dephosphorylation of<br />

Kv4.2. Finally, this reaction occurs both at the plasma membrane as well as inside the cell and<br />

does not change surface expression level of Kv4.2 by itself. These data indicate that Kv4.2<br />

phosphorylation is dynamically regulated in neurons and that neuronal activity and following<br />

activation of NMDA receptor is a strong regulator of Kv4.2. This activity dependent<br />

modification of Kv4.2 may underlie activity-dependent changes of dendritic excitability under<br />

physiological conditions.<br />

Disclosures: M. Nuriya, None; T. Ito, None; M. Yasui, None.<br />

Poster<br />

234. A-Type Potassium Channels<br />

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm

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