Functional uncoupling between Ca2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins

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

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Junctional membrane complexes (JMCs) composed of the plasma membrane and endoplasmic/sarcoplasmic reticulum seem to be a structural platform for channel crosstalk. Junctophilins (JPs) contribute to JMC formation by spanning the sarcoplasmic reticulum membrane and binding with the plasma membrane in muscle cells. In this article, we report that mutant JP double-knockout (JP-DKO) mice lacking neural JP subtypes exhibited an irregular hindlimb reflex and impaired memory. Electrophysiological experiments indicated that the activation of small-conductance Ca2+-activated K+ channels responsible for afterhyperpolarization in hippocampal neurons requires endoplasmic reticulum Ca2+ release through ryanodine receptors, triggered by NMDA receptor-mediated Ca2+ influx. We propose that in JP-DKO neurons lacking afterhyperpolarization, the functional communications between NMDA receptors, ryanodine receptors, and small-conductance Ca2+-activated K+ channels are disconnected because of 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.

Original languageEnglish
Pages (from-to)10811-10816
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number28
DOIs
Publication statusPublished - 2006 Jul 11

Keywords

  • Hippocampus
  • Learning and memory
  • Long-term potentiation
  • Ryanodine receptor
  • SK channel

ASJC Scopus subject areas

  • General

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