| First Author | Kyle BD | Year | 2013 |
| Journal | Sci Rep | Volume | 3 |
| Pages | 2447 | PubMed ID | 23945775 |
| Mgi Jnum | J:207798 | Mgi Id | MGI:5559649 |
| Doi | 10.1038/srep02447 | Citation | Kyle BD, et al. (2013) The large conductance, calcium-activated K+ (BK) channel is regulated by cysteine string protein. Sci Rep 3:2447 |
| abstractText | Large-conductance, calcium-activated-K(+) (BK) channels are widely distributed throughout the nervous system, where they regulate action potential duration and firing frequency, along with presynaptic neurotransmitter release. Our recent efforts to identify chaperones that target neuronal ion channels have revealed cysteine string protein (CSPalpha) as a key regulator of BK channel expression and current density. CSPalpha is a vesicle-associated protein and mutations in CSPalpha cause the hereditary neurodegenerative disorder, adult-onset autosomal dominant neuronal ceroid lipofuscinosis (ANCL). CSPalpha null mice show 2.5 fold higher BK channel expression compared to wild type mice, which is not seen with other neuronal channels (i.e. Cav2.2, Kv1.1 and Kv1.2). Furthermore, mutations in either CSPalpha's J domain or cysteine string region markedly increase BK expression and current amplitude. We conclude that CSPalpha acts to regulate BK channel expression, and consequently CSPalpha-associated changes in BK activity may contribute to the pathogenesis of neurodegenerative disorders, such as ANCL. |
