Open AccessCysteine String Protein Limits Expression of the Large Conductance, Calcium-Activated K+ (BK) Channel
Author(s) -
Eva Ahrendt,
Barry D. Kyle,
Andrew P. Braun,
Janice E. A. Braun
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0086586
Subject(s) - bk channel , calcium activated potassium channel , biophysics , n type calcium channel , neurotransmission , microbiology and biotechnology , chemistry , voltage dependent calcium channel , biology , calcium , biochemistry , t type calcium channel , potassium channel , receptor , organic chemistry
Large-conductance, calcium-activated K + (BK) channels are widely distributed throughout the nervous system and play an essential role in regulation of action potential duration and firing frequency, along with neurotransmitter release at the presynaptic terminal. We have previously demonstrated that select mutations in cysteine string protein (CSPα), a presynaptic J-protein and co-chaperone, increase BK channel expression. This observation raised the possibility that wild-type CSPα normally functions to limit neuronal BK channel expression. Here we show by Western blot analysis of transfected neuroblastoma cells that when BK channels are present at elevated levels, CSPα acts to reduce expression. Moreover, we demonstrate that the accessory subunits, BKβ4 and BKβ1 do not alter CSPα-mediated reduction of expressed BKα subunits. Structure-function analysis reveals that the N-terminal J-domain of CSPα is critical for the observed regulation of BK channels levels. Finally, we demonstrate that CSPα limits BK current amplitude, while the loss-of-function homologue CSPα HPD-AAA increases BK current. Our observations indicate that CSPα has a role in regulating synaptic excitability and neurotransmission by limiting expression of BK channels.