Submitted on April 10, 2007
Accepted on March 26, 2008
Increasing extracellular potassium results in subthalamic neuron activity resembling that seen in a 6-hydroxydopamine lesion
Ulf Strauss1*, Fu-Wen Zhou2, Jeannette Henning3, Arne Battefeld1, Andreas Wree4, Rudiger Kohling5, Stefan Jean Pierre Haas4, Reiner Benecke3, Arndt Rolfs3, and Ulrike Gimsa6
1 Institute of Cell- and Neurobiology, Charite-University Medical School Berlin, Berlin, Germany
2 Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee, United States
3 Departmemnt of Neurology, University Rostock, Rostock, Germany
4 Institute of Anatomy, University Rostock, Rostock, Germany
5 Institute of Physiology, University Rostock, Germany
6 Research Unit Behavioral Physiology, Research Institute for the Biology of Fram Animals, Rostock, Germany
* To whom correspondence should be addressed. E-mail: ulf.strauss{at}charite.de.
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 two-fold 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 to non-lesioned rats. Various [K+]o (1.5 mM to 12.5 mM) were applied to in vitro slice preparations of three experimental groups of STN slices from non-lesioned control rats, ipsilateral hemispheres, and contralateral hemispheres of lesioned rats. The majority of STN neurons of non-lesioned rats and in slices contralateral to the lesion fired spontaneously, predominantly in a regular pattern, while 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 post-train AHP. Lesion effects in ipsilateral neurons at physiological [K+]o resembled the effects of elevated [K+]o in non-lesioned 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.
