Figure 2. A hydrodynamic model of glioma cell migration.

a | Glioma cells encounter spatial barriers (for example, other cells) as they migrate along blood vessels through the brain. Gliomas express various channels, including Cl⁻ channel protein 3 (ClC3; a voltage-gated Cl⁻ channel), Ca²⁺-activated K⁺ channel KCa3.1 and aquaporins. b | Upon stimulation of G protein-coupled receptors (GPCRs), there is a rise in intracellular Ca²⁺ concentration ([Ca²⁺]_i) in glioma cells, leading to Ca²⁺-dependent activation of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII)-dependent ClC3 and KCa3.1 channel opening. This leads to the efflux of Cl⁻ and K⁺, obligating water to flow down its osmotic gradient and leave the cell. This volume decrease enables glioma cells to decrease cytoplasmic volume and squeeze into small spaces. c | After passing a spatial barrier, glioma cells can regain volume through ion influx through the Na⁺–K⁺–Cl⁻ cotransporter 1 (NKCC1) and acid-sensing ion channel 1 (ASIC1). BK, bradykinin.