title: Intron retention facilitates splice variant diversity in calcium-activated big potassium channel populations.
abstract: 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.
authors.affiliation: Department of Pharmacology, Penn Genome Frontiers Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Bell
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Miyashiro
authors.forename: Jai-Yoon
authors.initials: JY
authors.lastname: Sul
authors.forename: Peter T
authors.initials: PT
authors.lastname: Buckley
authors.forename: Miler T
authors.initials: MT
authors.lastname: Lee
authors.forename: Ron
authors.initials: R
authors.lastname: McCullough
authors.forename: Jeanine
authors.initials: J
authors.lastname: Jochems
authors.forename: Junhyong
authors.initials: J
authors.lastname: Kim
authors.forename: Charles R
authors.initials: CR
authors.lastname: Cantor
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Parsons
authors.forename: James H
authors.initials: JH
authors.lastname: Eberwine
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D003712:Dendrites; D006624:Hippocampus / Q000166:cytology; D007438:Introns / Q000235:genetics*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*; D009474:Neurons; D012333:RNA, Messenger; D051381:Rats
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D012333:RNA, Messenger