Functional Uncoupling Between Ca2+ Release and Afterhyperpolarization in Mutant Hippocampal Neurons Lacking Junctophilins

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Jul 1

PMID 16809425

Citations 46

Authors

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

Affiliations

Soon will be listed here.

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 Ca(2+)-activated K(+) channels responsible for afterhyperpolarization in hippocampal neurons requires endoplasmic reticulum Ca(2+) release through ryanodine receptors, triggered by NMDA receptor-mediated Ca(2+) influx. We propose that in JP-DKO neurons lacking afterhyperpolarization, the functional communications between NMDA receptors, ryanodine receptors, and small-conductance Ca(2+)-activated K(+) channels are disconnected because of JMC disassembly. Moreover, JP-DKO neurons showed an impaired long-term potentiation and hyperactivation of Ca(2+)/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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