title: Extracellular Potassium and Seizures: Excitation, Inhibition and the Role of Ih.
abstract: Seizure activity leads to increases in extracellular potassium concentration ([K[Formula: see text]]o), which can result in changes in neuronal passive and active membrane properties as well as in population activities. In this study, we examined how extracellular potassium modulates seizure activities using an acute 4-AP induced seizure model in the neocortex, both in vivo and in vitro. Moderately elevated [K[Formula: see text]]o up to 9[Formula: see text]mM prolonged seizure durations and shortened interictal intervals as well as depolarized the neuronal resting membrane potential (RMP). However, when [K[Formula: see text]]o reached higher than 9[Formula: see text]mM, seizure like events (SLEs) were blocked and neurons went into a depolarization-blocked state. Spreading depression was never observed as the blockade of ictal events could be reversed within 1-2[Formula: see text]min after the raised [K[Formula: see text]]o was changed back to control levels. This concentration-dependent dual effect of [K[Formula: see text]]o was observed using in vivo and in vitro mouse brain preparations as well as in human neocortical tissue resected during epilepsy surgery. Blocking the Ih current, mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, modulated the elevated [K[Formula: see text]]o influence on SLEs by promoting the high [K[Formula: see text]]o inhibitory actions. These results demonstrate biphasic actions of raised [K[Formula: see text]]o on neuronal excitability and seizure activity.
authors.affiliation: 1 Departments of Medicine (Neurology) and Physiology, University Health Network, University of Toronto, Toronto, M5T 2S8, Ontario, Canada.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1 Departments of Medicine (Neurology) and Physiology, University Health Network, University of Toronto, Toronto, M5T 2S8, Ontario, Canada.
authors.forename: Suzie
authors.initials: S
authors.lastname: Dufour
authors.affiliation: 2 Division of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, M5T 2S8, Ontario, Canada.
authors.forename: Taufik A
authors.initials: TA
authors.lastname: Valiante
authors.affiliation: 3 Departments of Medicine (Neurology) and Physiology, University Health Network, University of Toronto, Institute of Biomaterials and Biomedical Engineering University of Toronto, Toronto, M5T 2S8, Ontario, Canada.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Carlen
mesh_terms: D000328:Adult; D000818:Animals; D038481:Anterior Temporal Lobectomy; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D004195:Disease Models, Animal; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D012640:Seizures / Q000188:drug therapy / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D011188:Potassium
keywords: Ih; Potassium; excitation; inhibition; seizures