Montelukast activation of BK (Slo1) channels: Role of the β accessory subunits.

ORSI, F; MILESI, V; MARTÍN, P

Congreso; XLIX Reunión Anual SAB; 2021

Sociedad Argentina de Biofísica

The large conductance voltage- and Ca2+- dependent K+ channel (BK channel) has beenproposed as a possible pharmacological target in smooth muscle and central nervoussystem pathologies. Recently, the channel modulation through its β accessory subunitsemerged as the key to obtaining compounds showing a tissue selective activity. It hasbeen shown that leukotriene B4 activates the BK channel only in presence of β1. So, wehypothesize that Montelukast (MTK), a leukotriene receptor antagonist, can share thisproperty. Here, using the patch-clamp technique in the inside-out configuration, westudied the effect of MTK on the BK channel expressed in HEK cells with or withoutdifferent β subunits (β1, β2, and β4). 1 μM MTK slightly activated BK channel expressedwithout any β subunits: MTK changed the voltage dependence of channel activation (leftshift of the G-V curve, ΔV1/2= -10.8 ± 3.7 mV; n=3; p