Neocortical in vivo focal and spreading potassium responses and the influence of astrocytic gap junctional coupling

Abstract

Raised extracellular potassium ion (K+) concentration is associated with several disorders including migraine, stroke, neurotrauma and epilepsy. K+ spatial buffering is a well-known mechanism for extracellular K+ regulation/distribution. Astrocytic gap junction-mediated buffering is a controversial candidate for K+ spatial buffering. To further investigate the existence of a K+ spatial buffering and to assess the involvement of astrocytic gap junctional coupling in K+ redistribution, we hypothesized that neocortical K+ and concomitant spreading depolarization (SD)-like responses are controlled by powerful local K+ buffering mechanisms and that K+ buffering/redistribution occurs partially through gap junctional coupling. Herein, we show, in vivo, that a threshold amount of focally applied KCl is required to trigger local and/or distal K+ responses, accompanied by a SD-like response. This observation indicates the presence of powerful local K+ buffering which mediates a rapid return of extracellular K+ to the baseline. Application of gap junctional blockers, carbenoxolone and Gap27, partially modulated the amplitude and shape of the K+ response and noticeably decreased the velocity of the spreading K+ and SD-like responses. Opening of gap junctions by trimethylamine, slightly decreased the amplitude of the K+ response and markedly increased the velocity of redistribution of K+ and SD-like events. We conclude that spreading K+ responses reflect powerful local K+ buffering mechanisms which are partially modulated by gap junctional communication. Gap junctional coupling mainly affected the velocity of the K+ and SD-like responses.