新着情報

ジャンクトフィリンと記憶学習の関連解析 (2006. 6)

Functional uncoupling between Ca2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins (PNAS 103, 10811-10816, 2006.)

Shigeki Moriguchi, Miyuki Nishi, Shinji Komazaki, Hiroyuki Sakagami, Taisuke Miyazaki, Haruko Masumiya, Sin-ya Saito, Masahiko Watanabe, Hisatake Kondo, Hiromu Yawo, Kohji Fukunaga and Hiroshi Takeshima

Junctional membrane complexes (JMCs) composed of the plasma membrane (PM) and endoplasmic/sarcoplasmic reticulum (ER/SR) seem to be a structural platform for channel crosstalk. Junctophilins (JPs) contribute to JMC formation by spanning the SR membrane and binding with the PM in muscle cells. Here we report mutant (JP-DKO) mice lacking neural JP subtypes, which exhibited an irregular hindlimb reflex and impaired memory. Electrophysiological experiments indicated that the activation of small-conductance Ca2+-activated K+ (SK) channels responsible for afterhyperpolarization (AHP) in hippocampal neurons requires ER Ca2+ release through ryanodine receptors (RyRs), triggered by N-methyl D-aspartate receptor (NMDAR)-mediated Ca2+ influx. We propose that in JP-DKO neurons lacking AHP, the functional communications between NMDARs, RyRs and SK channels were disconnected due to JMC disassembly. Moreover, JP-DKO neurons showed an impaired long-term potentiation and hyperactivation of Ca2+/calmodulin-dependent protein kinase II. Therefore, JPs seem to have an essential role in neural excitability fundamental to plasticity and integrated functions.

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