Intron retention facilitates splice variant diversity in calcium-activated big potassium channel populations

被引：49

作者：

Bell, Thomas J. ^{[2
]}

Miyashiro, Kevin Y. ^{[2
]}

Sul, Jai-Yoon ^{[2
]}

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

Lee, Miler T. ^{[3
,4
]}

McCullough, Ron ^{[1
]}

Jochems, Jeanine ^{[2
]}

Kim, Junhyong ^{[3
,4
]}

Cantor, Charles R. ^{[1
]}

Parsons, Thomas D. ^{[5
,6
]}

Eberwine, James H. ^{[2
,3
]}

机构：

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

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

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

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

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

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

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 49期

基金：

美国国家卫生研究院;

关键词：

HIPPOCAMPAL PYRAMIDAL CELLS; LARGE-CONDUCTANCE; K+ CHANNELS; NEURONS; SUBUNIT; EXCITABILITY; BRAIN; REPOLARIZATION; EXPRESSION; TERMINALS;

D O I：

10.1073/pnas.1015264107

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：

We report that the stress axis-regulated exon (STREX)-containing calcium-activated big potassium (BKCa) channel splice variant expression and physiology are regulated in part by cytoplasmic splicing and intron retention. NextGen sequencing of the mRNA complement of pooled hippocampal dendrite samples found intron 17a (i17a), the intron immediately preceding STREX, in the BKCa mRNA. Further molecular analyses of i17a revealed that the majority of i17a-containing BKCa channel mRNAs associate with STREX. i17a siRNA treatment followed by STREX protein immunocytochemistry demonstrated both reduced levels and altered subcellular distribution of STREX-containing BKCa channel protein. Selective reduction of i17a-BKCa or STREX-BKCa mRNAs induced similar changes in the burst firing properties of hippocampal neurons. Collectively, these data show that STREX splice variant regulation via cytoplasmic splicing and intron retention helps generate STREX-dependent BKCa current diversity in hippocampal neurons.

引用

页码：21152 / 21157

页数：6

共 31 条

[21] The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells [J].