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Modulation of hSlo BK current inactivation by fatty acid esters of CoA
Author(s) -
Sun Xiaolu,
Yao Hang,
Zhou Dan,
Gu Xiang,
Haddad Gabriel G.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.05083.x
Subject(s) - chemistry , biophysics , fatty acid , biochemistry , peptide , biology
Lipid metabolism influences membrane proteins, including ion channels, in health and disease. Fatty acid esters of CoA are important intermediates in fatty acid metabolism and lipid biosynthesis. In the present study, we examined the effect of acyl‐CoAs on hSlo BK currents. Arachidonoyl‐CoA (C 20 ‐CoA) induced β2‐dependent inhibition of hSlo ‐α current when applied intracellularly but not extracellularly. This action was also mimicked by other long‐chain acyl‐CoAs such as oleoyl‐CoA (C 18 ‐CoA) and palmitoyl‐CoA (C 16 ‐CoA), but not acetyl‐CoA (C 2 ‐CoA, shorter chain), suggesting that the length of acyl chains, rather than CoA headgroups, is critical. When hSlo ‐α inactivation was induced by a free synthetic cationic β2 NH2‐terminus inactivation ball peptide, long‐chain acyl‐CoAs inhibited hSlo ‐α current and facilitated inactivation. The precursor fatty acids also facilitated the ball peptide‐induced inactivation in a chain length‐dependent manner, whereas sphingosine (positively charged) slowed this inactivation. When the β2‐induced inactivation was compared with that of the ball peptide, there was a negative shift in the steady state inactivation, slower recovery, and a reduced voltage‐dependence of inactivation onset. These data suggest that electrostatic interactions with the cytosolic inactivation domain of β2 mediate acyl‐CoA modulation of BK currents. BK channel inactivation may be a specific target for lipid modulation in physiological and pathophysiological conditions.