Mathematical Biology Seminar

Karen Wilcox
Neuroscience, University of Utah
Wednesday April 28, 2010

The M -Channel and Epilepsy: Mutations, Mice and Medicine

Abstract: The M-type K+ current [IK(M)] activates in response to membrane depolarization and regulates neuronal excitability. Mutations in two subunits (KCNQ2 and KCNQ3; Kv7.2 and Kv7.3) that underlie the M-channel cause the human seizure disorder Benign Familial Neonatal Convulsions (BFNC), presumably by reducing IK(M) function. While numerous studies have provided evidence for the inhibitory role of normally functioning M-channels in key brain structures related to seizures and epileptogenesis, the BFNC sequelae from mutation to seizure and ultimately to remission is likely very complex. In an effort to determine the role of the KCNQ mutations in epilepsy, our lab has investigated M-channel function in a number of mouse models with either spontaneous or targeted deletions in the Kcnq2 or Kcnq3 genes. The approach of combining whole-animal behavior, pharmacology and single-cell biophysics in mouse models of BFNC has helped solidify the link between attenuated IK(M) function, increased seizure susceptibility that result from Kcnq2 and Kcnq3 mutations, and the role of the M-channel as a target for novel anticonvulsants.