Modulating neocortical spatiotemporal potassium dynamics: effects on spreading depression

Ebrahim Amini, Azin  1, 2  ;   Paolo Bazzigaluppi   1, 3  ;   Iliya Weisspapir   1  ;   Bojana Stefanovic   3  ;   Peter L. Carlen  1, 2    

1.   Fundamental Neurobiology, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada;    2.   Department of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada;    3.   Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada   

Extracellular potassium ion concentration ([K]e) is tightly regulated throughout the brain because it has a major impact on brain functionality. Potassium concentration is disrupted in many brain diseases such as stroke and epilepsy. My project is designed base on a well-developed experimental platform to investigate the effects of extracellular potassium redistribution in physiological states.

All experiments were conducted in vivo in mouse neocortex. 2 double-barreled K-sensitive electrodes coupled with local field potential(LFP) electrodes were placed 4 mm apart. 50mM KCl solution was injected focally closer to one of the K-LFP electrodes. [K]e levels and LFP were measured in two different scenarios: 1) Pharmacological intervention (Gap junction blockage) 2) Optical intervention (optogentics).

Focally increased [K]e was associated with a transient depolarization which in turn spreads into neighboring tissues so called spreading depolarization. Gap junctional blockade in the peri-injection site simultaneously increased the amplitude and duration of the local [K]e response, and the local field response was greatly prolonged. While in the remote injection site, [K]e response was decreased after gap junctional blockage application. Optical stimulation decreased the [K]e both in the peri-injection and remote site.

Our preliminary results are evidence of slow K redistribution (take for minutes) throughout the astrocytic syncytium which is partly mediated via astrocytic gap junctions. Potassium redistribution across a large area of the cortex is not a well-studied area because most studies have limited their focus on focal potassium dynamics. In this project we are addressing this gap using novel tools to elucidate potassium redistribution dynamics.