MONTELUKAST ACTIVATES BK (SLO1) CHANNELS ASSOCIATED WITH THE Β4 ACCESSORY SUBUNIT AND EMERGES AS A PHARMACOLOGICAL TOOL TO REDUCE HIPPOCAMPAL EXCITABILITY

ORSI, F; MONAT, J; MILESI, V; RAINGO, J; MARTÍN, P

Mar del Plata

Congreso; Reunión anual de Sociedades de Biociencias; 2022

SAIC - SAI - SAFIS

Different β accessory subunits are associated with the large conductance voltage- and Ca2+- dependent K+ channel (BK channel) in a tissue-specific manner. In particular, BK channel/β4 subunits complexes (α/β4) control neuronal excitability in granule cells of the hippocampal dentate gyrus (GCDG) and, β4 deficient mice display neuronal hyperexcitability, a phenotype associated with the temporal lobe epilepsy (TLE). Thus, compounds that increase α/β4 activity are of great interest for improving epilepsy treatment. Then, based on the activating effect of LTB1 on BK channel associated with β1 subunit, we explore the effect of Montelukast (MTK) on this channel heterologously expressed in HEK cells with or without its β accessory subunits (β1, β2, and β4). MTK is a CysLT1 receptor ligand clinically used as an anti-asthmatic drug that could share the affinity properties with the LTB1. Using the patch clamp technique in voltage clamp we found that MTK shifts the activation curves of α/β1 and α/β4 to more hyperpolarized voltages in a concentration-dependent manner (300 nM MTK: ΔV1/2 (α/β1)= -54.4 mV ±8.4; n=6; p