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+?1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+?4 channels were just as well activated by DHA as vascular Slo1+?1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+?2, Slo1+LRRC26 (?1), and Slo1 channels without auxiliary subunits. Mutagenesis of ?1, ?2, and ?4 showed that the large effect of DHA in Slo1+?1 and Slo1+?4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the ?1 and ?4 subunits. Transfer of this amino acid pair from ?1 or ?4 to ?2 introduces a large response to DHA in Slo1+?2. The presence of a pair of oppositely charged residues at the aforementioned positions in ? 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.

SUBMITTER: Hoshi T 

PROVIDER: S-EPMC3607020 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature