The large-conductance Ca(2+)-activated K(+) channel interacts with the apolipoprotein ApoA1.
Owing to the multifaceted functions of the large conductance Ca(2+)-activated K(+) channel (BK), identification of protein-protein interactions is essential in determining BK regulation. A yeast two-hybrid screening of a cochlear cDNA library revealed a BK-ApoA1 interaction. Patch clamp recordings of excised membrane patches from transfected HEK293 cells showed that ApoA1 inhibits the BK alpha-subunit by significantly increasing activation and deactivation times, and shifting half-activation voltage to more positive potentials. Reciprocal coimmunoprecipitations verified the BK-ApoA1 interaction using excised sensory epithelium and ganglia. Additionally, immunocolocalization studies revealed BK and ApoA1 expression in both receptor cells and auditory neurons. These data suggest new avenues of investigation, given the importance of apolipoproteins in neurological diseases.
Sokolowski
Bernd
B
Dept. of Otolaryngology-HNS, University of South Florida, Tampa, 33612, USA. bsokolow@health.usf.edu
Duncan
R Keith
RK
Chen
Stephanie
S
Karolat
Jörg
J
Kathiresan
Thandavarayan
T
Harvey
Margaret
M
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens; D003051:Cochlea / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000378:metabolism*; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D016632:Apolipoprotein A-I; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits