Rosebrugh Bldg, Toronto, ON M5S 3G9
Room: RS 211
Regulation and spread of brain extracellular potassium concentration ([Ke]) is disrupted in many conditions, including epilepsy, brain trauma, migraine and stroke. Focally increased [Ke] causes a transient spreading depolarization, which, when sufficiently large, depresses local metabolism and neuronal activity, becoming a spreading depression (SD). Also we know that neighboring glia are connected to each other via gap junctions thereby they can communicate to one another. Goal of this project is to elucidate the effects of modulating neocortical local [Ke] and its spatiotemporal redistribution on local and distal [Ke] transients both in Physiological and pathological states. we hypothesized that the slow spread and redistribution of K is partly due to K ions passing via inter-glia gap junctions, and partly due to local diffusion from the area of initial higher [Ke] to more distal neocortical regions.
We utilized novel K measuring systems to study mouse cerebral neocortex in vivo, using double-barreled K-sensitive recording electrodes, which were located 4mm apart, coupled with local field potential recordings. In this study we looked both at normal and pathological conditions. Pathological condition was created by increasing [Ke] via focal injection of Kcl in the region.
Then we used two different types of interventions to elucidate the mechanisms underlying potassium redistribution: i) applied pharmacological tools to block gap junctions, ii) astrocytic membrane was optically hyperpolarized.
Results and conclusion:
We intended to elucidate the mechanisms underlying the slower K redistribution following focal [Ke] increase; as the result we observed that after gap junction blocker application, [Ke] was significantly increased in the peri-injection site and decreased in the remote site. SD was significantly prolonged after gap junctions were blocked. Illuminating light on the area transfected with the hyperpolarizing glia showed a significant decrease in resting [Ke].
In conclusion, spatial buffering of raised [Ke] is mediated through gap junctional communication. This study will further our understanding of the mechanisms and modulation of slow K redistribution in the neocortex, advancing brain therapeutics, particularly for focal epilepsy.