期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 6, 页码 1901-1906出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0711796105
关键词
dendrite; epilepsy; intron-retention; KCNMA1; local splicing
资金
- NIA NIH HHS [R37 AG009900, R01 AG009900, AG9900] Funding Source: Medline
- NIDCD NIH HHS [T32 DC005363, T32 DC 005363-01A1] Funding Source: Medline
- NIMH NIH HHS [MH58371] Funding Source: Medline
- OID CDC HHS [CH 41699] Funding Source: Medline
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.
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