Cl − and K + channels and their role in primary brain tumour biology

Profound cell volume changes occur in primary brain tumours as they proliferate, invade surrounding tissue or undergo apoptosis. These volume changes are regulated by the flux of Cl(-) and K(+) ions and concomitant movement of water across the membrane, making ion channels pivotal to tumour biology. We discuss which specific Cl(-) and K(+) channels are involved in defined aspects of glioma biology and how these channels are regulated. Cl(-) is accumulated to unusually high concentrations in gliomas by the activity of the NKCC1 transporter and serves as an osmolyte and energetic driving force for volume changes. Cell volume condensation is required as cells enter M phase of the cell cycle and this pre-mitotic condensation is caused by channel-mediated ion efflux. Similarly, Cl(-) and K(+) channels dynamically regulate volume in invading glioma cells allowing them to adjust to small extracellular brain spaces. Finally, cell condensation is a hallmark of apoptosis and requires the concerted activation of Cl(-) and Ca(2+)-activated K(+) channels. Given the frequency of mutation and high importance of ion channels in tumour biology, the opportunity exists to target them for treatment.