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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
DOWNREGULATION OF KV1.5 K+ CHANNELS BY THE AMP-ACTIVATED PROTEIN KINASE
Abstract number: P176
Mia
1
*S.
, Munoz
1
C., Pakladok
1
T., Siraskar
1
G., Voelkl
1
J., Alesutan
1
I., Lang
1
F.
1
University of Tuebingen, Department of Physiology, Tübingen, Germany
Background:
The voltage gated K+ channel Kv1.5 participates in the repolarization of a wide variety of cell types. Kv1.5 is downregulated during hypoxia, which is known to stimulate the energy-sensing AMP-activated serine/threonine protein kinase (AMPK). AMPK is a powerful regulator of nutrient transport and metabolism. Moreover, AMPK is known to downregulate several ion channels, an effect at least in part due to stimulation of the ubiquitin ligase Nedd4-2. The present study explored whether AMPK regulates Kv1.5.
Methods:
cRNA encoding Kv1.5 was injected into Xenopus oocytes with and without additional injection of wild-type AMPK (α1 β1γ1), of constitutively active γR70QAMPK (α1 β1γ1(R70Q)), of inactive mutant αK45RAMPK (α1(K45R)β1γ1), or of the ubiquitin ligase Nedd4-2. Kv1.5 activity was determined by two-electrode voltage-clamp. Moreover, Kv1.5 protein abundance in the cell membrane was determined by chemiluminescence and immunostaining with subsequent confocal microscopy.
Results:
coexpression of wild-type AMPKWT and constitutively active AMPKγR70Q, but not of inactive AMPKαK45R signifcantly reduced Kv1.5-mediated currents. Coexpression of constitutively active AMPKγR70Q further reduced Kv1.5 K+ channel protein abundance in the cell membrane. Co-expression of Nedd4-2 similarly downregulated Kv1.5-mediated currents.
Conclusions:
AMPK is a potent regulator of Kv1.5. AMPK inhibits Kv1.5 presumably in part by activation of Nedd4-2 with subsequent clearance of channel protein from the cell membrane.
To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :P176