Inhibition of Connexin 26 by the AMP-Activated Protein Kinase

Inhibition of Connexin 26 by the AMP-Activated Protein Kinase Connexins provide intercellular connections that allow passage of ions and small organic molecules. They clamp the cell membrane potential and cellular ion composition to that of neighboring cells. The cell membrane potential and ion composition of an energy-depleted cell could thus be maintained despite its compromised Na+/K+ activity. By the same token, however, the breakdown of ion gradients in that cell imposes an additional challenge to the neighboring cells, which may jeopardize their survival. Thus, timely closure of connexins may be critically important for the survival of those cells. Energy depletion stimulates the AMP-activated protein kinase (AMPK), a serine/threonine kinase that senses energy depletion and stimulates several cellular mechanisms to enhance energy production and to limit energy utilization. The present study explored whether AMPK regulates connexin 26. To this end, cRNA encoding connexin 26 was injected into Xenopus oocytes with and without additional injection of wild-type AMPK (α1β1γ1), of the constitutively active γR70QAMPK (α1β1γ1[R70Q]) or of the inactive mutant αK45RAMPK (α1[K45R]β1γ1). Connexin 26 activity was determined in dual-electrode voltage-clamp experiments. Moreover, connexin 26 abundance was determined in the oocyte cell membrane by chemiluminescence and confocal microscopy. As a result, connexin 26-mediated current and connexin 26 protein abundance were significantly decreased by coexpression of γR70QAMPK and, to a lower extent, by wild-type AMPK but not by αK45RAMPK. In conclusion, AMPK is a potent regulator of connexin 26. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Inhibition of Connexin 26 by the AMP-Activated Protein Kinase

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Publisher
Springer-Verlag
Copyright
Copyright © 2011 by Springer Science+Business Media, LLC
Subject
Life Sciences; Human Physiology ; Biochemistry, general
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-011-9353-y
Publisher site
See Article on Publisher Site

Abstract

Connexins provide intercellular connections that allow passage of ions and small organic molecules. They clamp the cell membrane potential and cellular ion composition to that of neighboring cells. The cell membrane potential and ion composition of an energy-depleted cell could thus be maintained despite its compromised Na+/K+ activity. By the same token, however, the breakdown of ion gradients in that cell imposes an additional challenge to the neighboring cells, which may jeopardize their survival. Thus, timely closure of connexins may be critically important for the survival of those cells. Energy depletion stimulates the AMP-activated protein kinase (AMPK), a serine/threonine kinase that senses energy depletion and stimulates several cellular mechanisms to enhance energy production and to limit energy utilization. The present study explored whether AMPK regulates connexin 26. To this end, cRNA encoding connexin 26 was injected into Xenopus oocytes with and without additional injection of wild-type AMPK (α1β1γ1), of the constitutively active γR70QAMPK (α1β1γ1[R70Q]) or of the inactive mutant αK45RAMPK (α1[K45R]β1γ1). Connexin 26 activity was determined in dual-electrode voltage-clamp experiments. Moreover, connexin 26 abundance was determined in the oocyte cell membrane by chemiluminescence and confocal microscopy. As a result, connexin 26-mediated current and connexin 26 protein abundance were significantly decreased by coexpression of γR70QAMPK and, to a lower extent, by wild-type AMPK but not by αK45RAMPK. In conclusion, AMPK is a potent regulator of connexin 26.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Mar 12, 2011

References

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