title: Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA.
abstract: Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.
authors.affiliation: Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA. hoshi@hoshi.org
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hoshi
authors.forename: Yutao
authors.initials: Y
authors.lastname: Tian
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Heinemann
authors.forename: Shangwei
authors.initials: S
authors.lastname: Hou
mesh_terms: D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D009928:Organ Specificity / Q000502:physiology; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D046912:Multiprotein Complexes; D021122:Protein Subunits; D004281:Docosahexaenoic Acids