Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit

Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca2+- and voltage-dependent K+ channel (BK) in vascular smooth muscle depending on the expression of the auxiliary beta 1 subunit. Here, using the patch-clamp technique on BK channel co-expressed with beta 1 subunit in a hetemlogous cell expression system, we analyzed whether AA modifies the three functional modules involved in the channel gating: the voltage sensor domain (VSD), the pore domain (PD), and the intracellular calcium sensor domain (CSD). We present evidence that AA activates BK channel in a direct way, inducing VSD stabilization on its active configuration observed as a significant left shift in the Q-V curve obtained from gating currents recordings. Moreover, AA facilitates the channel opening transitions when VSD are at rest, and the CSD are unoccupied. Furthermore, the activation was independent of the intracellular Ca2+ concentration and reduced when the BK channel was co-expressed with the Y74A mutant of the beta 1 subunit. These results allow us to present new insigths in the mechanism by which AA modulates BK channels co-expressed with its auxiliary beta 1 subunit.

Automated summary

Arachidonic acid (AA) directly activates BK channels co-expressed with the auxiliary beta 1 subunit, stabilizing the voltage sensor domain (VSD) on its active configuration and facilitating channel opening transitions when VSD are at rest and CSD are unoccupied. The activation is independent of intracellular Ca2+ concentration and reduced when co-expressed with the Y74A mutant of the beta 1 subunit.