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Ion Channels and Excitable Membranes

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Modulation of TASK Currents by the Activity of cGMP-Dependent Protein Kinase

  • P2-011
  • 齋藤 充 / Mitsuru Saito:1 田中 千惠 / Chie Tanaka:1 古谷 和春 / Kazuharu Furutani:2 岡澤 慎 / Makoto Okazawa:3 豊田 博紀 / Hiroki Toyoda:1 佐藤 元 / Hajime Sato:1 倉智 嘉久 / Yoshihisa Kurachi:2 姜 英男 / Youngnam Kang:1 
  • 1:大阪大院・歯・高次脳口腔機能 / Dept. Neurosci. & Oral Physiol., Osaka Univ. Grad. Sch. Dent., Osaka, Japan 2:大阪大院・医・分子細胞薬理 / Div. Mol. Cell. Physiol., Osaka Univ. Grad. Sch. Med., Osaka, Japan 3:国立循環器病セ研・血管生理 / Dept. Vasc. Physiol., Nat. Cereb. & Cardiovasc. Center Res. Inst., Osaka, Japan 

Leak K+ conductances generated by TWIK-related acid-sensitive K+ channels (TASK) types 1 and 3 are crucial for determining the resting membrane potential (Vr) and input resistance (IR) in neurons. A in situ hybridization analysis in rats showed that both mRNAs of the TASK1 and TASK3 channels densely express in the trigeminal motor nucleus (Karschin et al., 2001). Therefore, modulation of TASK1 and TASK3 conductances is thought to play important roles in regulating the rank-ordered recruitment of trigeminal motoneurons observed during isometric contraction of jaw closing muscles. However, only a few endogenous modulators for TASK1 and TASK3 channels in neurons were found. We previously demonstrated that activation and inhibition of cGMP-dependent protein kinase (PKG) respectively upregulate and downregulate TASK1 channels heterologously expressed in PKG-loaded HEK293 cells at physiological pH, by causing shifts in the Kd in the acidic and basic directions, respectively (Toyoda et al., J. Neurosci., 2010). In the present study, PKG activation by application of 8-Br-cGMP hyperpolarized Vr and reduced IR in the trigeminal motoneurons with small somata that predominantly express TASK1 but not TASK3, in the rat. In contrast, 8-Br-cGMP application did not necessarily cause such changes in Vr and IR in the large trigeminal motoneurons that richly express TASK1 in the somata and TASK3 in the dendrites, suggesting that TASK3 is downregulated by PKG activation at least at physiological pH. We examined this possibility in the heterologous expression systems of mammalian cell lines (HEK293, COS-7, CHO, and A9) transfected with TASK3 cDNA and Xenopus laevis oocytes injected with TASK3 cRNA. Among those, we successfully recorded TASK3 currents from the A9 cells and Xenopus oocytes, and examined the effects of 8-Br-cGMP on TASK3 currents.

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