The Journal of Neuroscience, September 1, 2001, 21(17):6635-6643
Calmodulin Kinase Pathway Mediates the K+-Induced
Increase in Gap Junctional Communication between Mouse Spinal Cord
Astrocytes
Mara H.
De Pina-Benabou1, 2,
Miduturu
Srinivas2,
David
C.
Spray2, and
Eliana
Scemes2
1 Department of Physiology, Bioscience Institute,
University of Sao Paulo, Sao Paulo, CP-11461, Brazil, and
2 Department of Neuroscience, Albert Einstein College of
Medicine, Bronx, New York 10461
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.
Key words:
glia; potassium; dye coupling; junctional conductance; Ca2+-calmodulin; connexin; Lucifer yellow
spread
Copyright © 2001 Society for Neuroscience 0270-6474/01/21176635-09$05.00/0
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