Calmodulin kinase pathway mediates the K+-induced increase in gap junctional communication between mouse spinal cord astrocytes

Astrocytes are coupled to one another by gap junction channels that allow t he diffusion of ions and small molecules throughout the interconnected sync ytium. In astrocytes, gap junctions are believed to participate in spatial buffering removing the focal excess of potassium resultant from intense neu ronal activity by current loops through the syncytium and are also implicat ed in the propagation of astrocytic calcium waves, a form of extraneuronal signaling. Gap junctions can be modulated by several factors, including ele vation of extracellular potassium concentration. Because K+ elevation is a component of spinal cord injury, we evaluated the extent to which cultured spinal cord astrocytes is affected by K+ levels and obtained evidence sugge sting that a Ca2+-calmodulin (CaM) protein kinase is involved in the K+-ind uced increased coupling. Exposure of astrocytes to high K+ solutions induce d a dose-dependent increase in dye coupling; such increased coupling was gr eatly attenuated by reducing extracellular Ca2+ concentration, prevented by nifedipine, and potentiated by Bay-K-8644. These results indicate that K+- induced increased coupling is mediated by a signaling pathway that is depen dent on the influx of Ca2+ through L-type Ca2+ channels. Evidence supportin g the participation of the CaM kinase pathway on K+-induced increased coupl ing was obtained in experiments showing that calmidazolium and KN-93 totall y prevented the increase in dye and electrical coupling induced by high Ksolutions. Because no changes in connexin43 expression levels or distributi on were observed in astrocytes exposed to high K+ solutions, we propose tha t the increased junctional communication is related to an increased number of active channels within gap junction plaques.