Functional expression of the proton sensors ASIC1a, TMEM206, and OGR1 together with BK < sub > Ca < /sub > channels is associated with cell volume changes and cell death under strongly acidic conditions in DAOY medulloblastoma cells

In this study, using RT-qPCR, whole-cell patch clamp, and Ca2+-imaging, we uncovered several ion channels and a G protein-coupled receptor, which were regulated directly or indirectly by low extracellular pH in DAOY and UW228 medulloblastoma cells. Acidification directly activated acid-sensing ion channel 1a (ASIC1a), the proton-activated Cl- channel (PAC, ASOR, or TMEM206), and the proton-activated G protein-coupled receptor OGR1. The resulting Ca2+ signal secondarily activated the large conductance calcium-activated potassium channel (BKCa). Our analyses uncover a complex relationship of these transmembrane proteins in DAOY cells that resulted in cell volume changes and induced cell death under strongly acidic conditions. Collectively, our results suggest that these ion channels in concert with OGR1 may shape the growth and evolution of medulloblastoma cells in their acidic microenvironment.PMID:38627262 | DOI:10.1007/s00424-024-02964-7
Source: Pflugers Archiv : European Journal of Physiology - Category: Physiology Authors: Source Type: research