The large conductance, calcium-activated K+ (BK) channel is regulated by cysteine string protein.
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 (CSPα) as a key regulator of BK channel expression and current density. CSPα is a vesicle-associated protein and mutations in CSPα cause the hereditary neurodegenerative disorder, adult-onset autosomal dominant neuronal ceroid lipofuscinosis (ANCL). CSPα 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 CSPα's J domain or cysteine string region markedly increase BK expression and current amplitude. We conclude that CSPα acts to regulate BK channel expression, and consequently CSPα-associated changes in BK activity may contribute to the pathogenesis of neurodegenerative disorders, such as ANCL.
Department of Physiology and Pharmacology, The Libin Cardiovascular Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Barry D
BD
Kyle
Eva
E
Ahrendt
Andrew P
AP
Braun
Janice E A
JE
Braun
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005786:Gene Expression Regulation; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D014018:Tissue Distribution
D050956:HSP40 Heat-Shock Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008565:Membrane Proteins; C088460:cysteine string protein