The large conductance, calcium-activated K+ (BK) channel is regulated by cysteine string protein.

ABSTRACT: 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 (CSP?) as a key regulator of BK channel expression and current density. CSP? is a vesicle-associated protein and mutations in CSP? cause the hereditary neurodegenerative disorder, adult-onset autosomal dominant neuronal ceroid lipofuscinosis (ANCL). CSP? 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 CSP?'s J domain or cysteine string region markedly increase BK expression and current amplitude. We conclude that CSP? acts to regulate BK channel expression, and consequently CSP?-associated changes in BK activity may contribute to the pathogenesis of neurodegenerative disorders, such as ANCL.

SUBMITTER: Kyle BD 

PROVIDER: S-EPMC3744087 | biostudies-other | 2013

REPOSITORIES: biostudies-other