Regulation of a Large Conductance, Calcium-Activated Potassium (BK) Channel by J-Proteins

BK channels are K + channels that are widely distributed throughout the nervous system.The activity of presynaptic BK channels governs synaptic transmission by regulating the influx of extracellular calcium through voltagegated calcium channels.Until now, little is known about the molecular chaperone machinery that participates in the folding and degradation of BK channels.CSPα (cysteine string protein) is a synaptic vesicleassociated molecular chaperone that prevents activitydependent neuronal degeneration by unknown mechanisms.Using CAD cells that transiently or stably expressed in BK channel, we assessed the influence of CSPα a BK channel expression using Western Blot analyses.This study indicates that CSPα and related Jproteins interact with and changed BK channel expression.We demonstrate that the highly conserved HPD motif within the Jdomain is required for BK channel reduction.These results provide the first evidence that CSPα regulates BK channel expression and attribute a key role to CSPα in neurotransmission.