title: Increasing extracellular potassium results in subthalamic neuron activity resembling that seen in a 6-hydroxydopamine lesion.
abstract: Abnormal neuronal activity in the subthalamic nucleus (STN) plays a crucial role in the pathophysiology of Parkinson's disease (PD). Although altered extracellular potassium concentration ([K+]o) and sensitivity to [K+]o modulates neuronal activity, little is known about the potassium balance in the healthy and diseased STN. In vivo measurements of [K+]o using ion-selective electrodes demonstrated a twofold increase in the decay time constant of lesion-induced [K+]o transients in the STN of adult Wistar rats with a unilateral 6-hydroxydopamine (6-OHDA) median forebrain bundle lesion, employed as a model of PD, compared with nonlesioned rats. Various [K+]o concentrations (1.5-12.5 mM) were applied to in vitro slice preparations of three experimental groups of STN slices from nonlesioned control rats, ipsilateral hemispheres, and contralateral hemispheres of lesioned rats. The majority of STN neurons of nonlesioned rats and in slices contralateral to the lesion fired spontaneously, predominantly in a regular pattern, whereas those in slices ipsilateral to the lesion fired more irregularly or even in bursts. Experimentally increased [K+]o led to an increase in the number of spontaneously firing neurons and action potential firing rates in all groups. This was accompanied by a decrease in the amplitude of post spike afterhyperpolarization (AHP) and the amplitude and duration of the posttrain AHP. Lesion effects in ipsilateral neurons at physiological [K+]o resembled the effects of elevated [K+]o in nonlesioned rats. Our data suggest that changed potassium sensitivity due to conductivity alterations and delayed clearance may be critical for shaping STN activity in parkinsonian states.
authors.affiliation: Neurobiology, Department of Neurology, University of Rostock, Rostock, Germany. ulf.strauss@charite.de
authors.forename: Ulf
authors.initials: U
authors.lastname: Strauss
authors.forename: Fu-Wen
authors.initials: FW
authors.lastname: Zhou
authors.forename: Jeannette
authors.initials: J
authors.lastname: Henning
authors.forename: Arne
authors.initials: A
authors.lastname: Battefeld
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Köhling
authors.forename: Stefan Jean-Pierre
authors.initials: SJ
authors.lastname: Haas
authors.forename: Reiner
authors.initials: R
authors.lastname: Benecke
authors.forename: Arndt
authors.initials: A
authors.lastname: Rolfs
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gimsa
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D045604:Extracellular Fluid / Q000187:drug effects; D007839:Functional Laterality / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000473:pathology*; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020531:Subthalamic Nucleus / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D011188:Potassium