Association of Epithelial Na+ channel (ENaC) and Acid‐Sensitive Ion Channel (ASIC) Subunits with Lipid Rafts in High Grade Gliomas

Abstract

Malignant gliomas, the most common type of primary tumors of the central nervous system, are divided into four grades based on their degree of malignancy. Glioblastoma multiforme (GBM), Grade IV, is the most frequently occurring, most invasive, and has the worst prognostic outcome. Studies in our laboratory have established that high grade glioma cells express subunits of the Epithelial Na+ channel/Degenerin family, and that these cells also exhibit a basally active cation current which is not present in low grade tumor cells or normal astrocytes. The goal of our research is to characterize the pathways that regulate trafficking of this novel channel complex in gliomas by testing the hypothesis that this heteromeric channel complex is recruited to and assembled on lipid rafts prior to incorporation into the plasma membrane. By utilizing biochemical and biophysical methods, we have obtained data showing an association of the lipid raft markers caveolin‐1 and flottilin‐1 with ENaC and ASIC subunits. Cholesterol depletion experiments indicate decreased expression of these subunits in lipid raft fractions isolated from glioma cells. Overall, the results generated from these studies will provide important clues as to the physiological role of this current pathway in the biology of brain tumors. Research supported by NIH‐5T32DK7545‐23.