Cytoplasmic BKCa channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons

被引：59

作者：

Bell, Thomas J. ^{[3
]}

Miyashiro, Kevin Y. ^{[3
]}

Sul, Jai-Yoon ^{[3
,4
]}

McCullough, Ronald ^{[7
]}

Buckley, Peter T. ^{[2
,3
]}

Jochems, Jeanine ^{[3
]}

Meaney, David F. ^{[5
]}

Haydon, Phil ^{[4
]}

Cantor, Charles ^{[1
]}

Parsons, Thomas D. ^{[6
,8
]}

Eberwine, James ^{[2
,3
]}

机构：

[1] Sequenom Inc, San Diego, CA 92121 USA

[2] Univ Penn, Sch Med, Penn Genome Frontiers Inst, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA

[4] Univ Penn, Sch Med, Dept Neurosci, Philadelphia, PA 19104 USA

[5] Univ Penn, Sch Med, Dept Bioengn, Philadelphia, PA 19104 USA

[6] Univ Penn, Sch Med, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA

[7] Boston Univ, Program Mol & Cellular Biol & Biochem, Boston, MA 02215 USA

[8] Univ Penn, Sch Vet Med, New Bolton Ctr, Dept Clin Studies, Kennett Sq, PA 19348 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 06期

关键词：

dendrite; epilepsy; intron-retention; KCNMA1; local splicing;

D O I：

10.1073/pnas.0711796105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

High single-channel conductance K+ channels, which respond jointly to membrane depolarization and micromolar concentrations of intracellular Ca2+ ions, arise from extensive cell-specific alternative splicing of pore-forming a-subunit mRNAs. Here, we report the discovery of an endogenous BKCa channel alpha-subunit intron-containing mRNA in the cytoplasm of hippocampal neurons. This partially processed mRNA, which comprises approximate to 10% of the total BKCa channel a-subunit mRNAs, is distributed in 6 gradient throughout the somatodendritic space. We selectively reduced endogenous cytoplasmic levels of this intron-containing transcript by RNA interference without altering levels of the mature splice forms of the BKCa channel mRNAs. In doing so, we could demonstrate that changes in a unique BKCa channel alpha-subunit intron-containing splice variant mRNA can greatly impact the distribution of the BKCa channel protein to dendritic spines and intrinsic firing properties of hippocampal neurons. These data suggest a new regulatory mechanism for modulating the membrane properties and ion channel gradients of hippocampal neurons.

引用

页码：1901 / 1906

页数：6

共 43 条

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