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

Mara H. De Pina-Benabou, Miduturu Srinivas, David C. Spray, Eliana Scemes

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


Astrocytes are coupled to one another by gap junction channels that allow the diffusion of ions and small molecules throughout the interconnected syncytium. In astrocytes, gap junctions are believed to participate in spatial buffering removing the focal excess of potassium resultant from intense neuronal activity by current loops through the syncytium and are also implicated in the propagation of astrocytic calcium waves, a form of extraneuronal signaling. Gap junctions can be modulated by several factors, including elevation 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 suggesting that a Ca2+-calmodulin (CaM) protein kinase is involved in the K+-induced increased coupling. Exposure of astrocytes to high K+ solutions induced a dose-dependent increase in dye coupling; such increased coupling was greatly 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 dependent on the influx of Ca2+ through L-type Ca2+ channels. Evidence supporting the participation of the CaM kinase pathway on K+-induced increased coupling was obtained in experiments showing that calmidazolium and KN-93 totally prevented the increase in dye and electrical coupling induced by high K+ solutions. Because no changes in connexin43 expression levels or distribution were observed in astrocytes exposed to high K+ solutions, we propose that the increased junctional communication is related to an increased number of active channels within gap junction plaques.

Original languageEnglish (US)
Pages (from-to)6635-6643
Number of pages9
JournalJournal of Neuroscience
Issue number17
StatePublished - Sep 1 2001


  • Ca-calmodulin
  • Connexin
  • Dye coupling
  • Glia
  • Junctional conductance
  • Lucifer yellow spread
  • Potassium

ASJC Scopus subject areas

  • General Neuroscience


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