28 / 2021-07-20 11:25:18

Beta2-containing Slo1 channels discriminate among n-3, n-6, and n-9 polyunsaturated fatty acids

BK channel,polyunsaturated fatty acids,auxiliary subunits,gating

Long-chain polyunsaturated fatty acids are diverse in their structures and functional roles.  For example, n-3 and n-6 polyunsaturated fatty acids differ in the location of the first double bond counting from the methyl group end.  n-3 Docosahexaenoic acid regulates many molecular effectors including large-conductance Ca2+- and voltage-dependent K+ (Slo1 BK) channels.  Slo1 BK complexes composed of pore-forming Slo1 and auxiliary b1 subunits are activated both by n-3 docosahexaenoic and n-6 long-chain polyunsaturated fatty acids.  In contrast, only n-6 and n-9 fatty acids activate inactivating Slo1+beta2 channels and n-3 fatty acids are largely without effect.  The activating effect of the n-6 fatty acids persists in the absence of the inactivation mechanism mediated by the distal N-terminal residues but abolished by neutralization of the charged residues C-terminal to the distal inactivation domain of beta2. Beta2-containing Slo1 BK channels respond to fatty acids from different sources utilizing the charged residues in beta2 the N terminus.