NDLI: AMP-activated protein kinase regulates hERG potassium channel

Content Provider	Springer Nature Link
Author	Almilaji, Ahmad Muz, Carlos Elvira, Bernat Fajol, Abul Pakladok, Tatsiana Honisch, Sabina Shumilina, Ekaterina Lang, Florian Föller, Michael
Copyright Year	2013
Abstract	Besides their role in cardiac repolarization, human ether-a-go-go-related gene potassium (hERG) channels are expressed in several tumor cells including rhabdomyosarcoma cells. The channels foster cell proliferation. Ubiquitously expressed AMP-dependent protein kinase (AMPK) is a serine-/threonine kinase, stimulating energy-generating and inhibiting energy-consuming processes thereby helping cells survive periods of energy depletion. AMPK has previously been shown to regulate Na+/K+ ATPase, Na+/Ca2+ exchangers, Ca2+ channels and K+ channels. The present study tested whether AMPK regulates hERG channel activity. Wild type AMPK (α1β1γ1), constitutively active γR70QAMPK (α1β1γ1(R70Q)), or catalytically inactive αK45RAMPK (α1(K45R)β1γ1) were expressed in Xenopus oocytes with hERG. Tail currents were determined as a measure of hERG channel activity by two-electrode-voltage clamp. hERG membrane abundance was quantified by chemiluminescence and visualized by immunocytochemistry and confocal microscopy. Moreover, hERG currents were measured in RD rhabdomyosarcoma cells after pharmacological modification of AMPK activity using the patch clamp technique. Coexpression of wild-type AMPK and of constitutively active γR70QAMPK significantly downregulated the tail currents in hERG-expressing Xenopus oocytes. Pharmacological activation of AMPK with AICAR or with phenformin inhibited hERG currents in Xenopus oocytes, an effect abrogated by AMPK inhibitor compound C. γR70QAMPK enhanced the Nedd4-2-dependent downregulation of hERG currents. Coexpression of constitutively active γR70QAMPK decreased membrane expression of hERG in Xenopus oocytes. Compound C significantly enhanced whereas AICAR tended to inhibit hERG currents in RD rhabdomyosarcoma cells. AMPK is a powerful regulator of hERG-mediated currents in both, Xenopus oocytes and RD rhabdomyosarcoma cells. AMPK-dependent regulation of hERG may be particularly relevant in cardiac hypertrophy and tumor growth.
Starting Page	1573
Ending Page	1582
Page Count	10
File Format	PDF
ISSN	00316768
Journal	Pflügers Archiv
Volume Number	465
Issue Number	11
e-ISSN	14322013
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2013-05-29
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	K+ channels AMPK Rhabdomyosarcoma Patch clamp Cardiac hypertrophy Human Physiology
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Clinical Biochemistry

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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