title: Inhibition of connexin 26 by the AMP-activated protein kinase.
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 (γR70Q)AMPK (α1β1γ1[R70Q]) or of the inactive mutant (αK45R)AMPK (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 (γR70Q)AMPK and, to a lower extent, by wild-type AMPK but not by (αK45R)AMPK. In conclusion, AMPK is a potent regulator of connexin 26.
authors.affiliation: Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.forename: Mentor
authors.initials: M
authors.lastname: Sopjani
authors.forename: Carlos
authors.initials: C
authors.lastname: Munoz
authors.forename: Scott
authors.initials: S
authors.lastname: Fraser
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Kemp
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009865:Oocytes; D014981:Xenopus
chemical_list: D017630:Connexins; C000607045:GJB2 protein, Xenopus; D000072259:Connexin 26; D055372:AMP-Activated Protein Kinases