Identification of the volume-sensitive organic osmolyte/anion channel in human glial cells

Abstract

Cellular use of small organic solutes known as organic osmolytes for regulation of the volume of the cell is a universal biological phenomenon. During swelling, cells open an anion channel which allows for efflux of these solutes. This channel is known as the volume-sensitive organic osmolyte/anion channel (VSOAC). Anion channels with properties identical to VSOAC were found in human brain cells obtained following pediatric neurosurgical procedures. The tissues examined included tumors as well as putatively normal gray and white matter astrocytes. The cells activated an anion conductance when swollen by hypotonic shock. Baseline currents in these cells were generally small and increased up to 30-fold within 10 min following the onset of swelling. The anion channel activated by swelling was outwardly rectified and inactivated by depolarization, both characteristic of the VSOAC. These observations indicate that human glial cells and tumor cells activate VSOAC following cellular swelling. This suggests that organic osmolyte efflux can be modulated during brain swelling by pharmaceuticals which modulate VSOAC.