Defective potassium currents in ataxia telangiectasia fibroblasts

Similarities exist between the progressive cerebellar ataxia in ataxia tela ngiectasia (AT) patients and a number of neurodegenerative diseases in both mouse and man involving specific mutations in ion channels and/or ion chan nel activity. These relationships led us to investigate the possibility of defective ion channel activity in AT cells. We examined changes in the memb rane potential of AT fibroblasts in response to extracellular cation additi on and found that the ability of AT fibroblasts to depolarize in response t o increasing concentrations of extracellular K+ is significantly reduced wh en compared with control fibroblasts. Electrophysiological measurements per formed with a number of AT cell lines, as well as two matched sets of prima ry AT fibroblast cultures, reveal that outward rectifier K+ currents are la rgely absent in AT fibroblasts in comparison with control cells. These K+ c urrent defects can be corrected in AT fibroblasts transfected with the full -length ATM cDNA. These data implicate, for the first time, a role for ATM in the regulation of K+ channel activity and membrane potential.