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

ORSI, FEDERICO; MONAT JULIANA; MILESI, VERÓNICA; RAINGO JESICA; MARTIN PEDRO

Mar del Plata

Congreso; Reunión Conjunta de Sociedades de Biociencias SAI-SAIC-SAFIS 2022; 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 subunitscomplexes (α/β4) control neuronal excitability in granule cells of thehippocampal dentate gyrus (GCDG) and, β4 deficient mice displayneuronal 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 associatedwith β1 subunit, we explore the effect of Montelukast (MTK) on thischannel heterologously expressed in HEK cells with or without itsβ accessory subunits (β1, β2, and β4). MTK is a CysLT1 receptorligand clinically used as an anti-asthmatic drug that could share theaffinity properties with the LTB1. Using the patch clamp technique involtage 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