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

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.