AMPK activation with AICAR provokes an acute fall in plasma [K+].
AMP-activated protein kinase (AMPK), activated by an increase in intracellular AMP-to-ATP ratio, stimulates pathways that can restore ATP levels. We tested the hypothesis that AMPK activation influences extracellular fluid (ECF) K(+) homeostasis. In conscious rats, AMPK was activated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) infusion: 38.4 mg x kg bolus then 4 mg x kg(-1) x min(-1) infusion. Plasma [K(+)] and [glucose] both dropped at 1 h of AICAR infusion and [K(+)] dropped to 3.3 +/- 0.04 mM by 3 h, linearly related to the increase in muscle AMPK phosphorylation. AICAR treatment did not increase urinary K(+) excretion. AICAR lowered [K(+)] whether plasma [K(+)] was chronically elevated or lowered. The K(+) infusion rate needed to maintain baseline plasma [K(+)] reached 15.7 +/- 1.3 micromol K(+) x kg(-1) x min(-1) between 120 and 180 min AICAR infusion. In mice expressing a dominant inhibitory form of AMPK in the muscle (Tg-KD1), baseline [K(+)] was not different from controls (4.2 +/- 0.1 mM), but the fall in plasma [K(+)] in response to AICAR (0.25 g/kg) was blunted: [K(+)] fell to 3.6 +/- 0.1 in controls and to 3.9 +/- 0.1 mM in Tg-KD1, suggesting that ECF K(+) redistributes, at least in part, to muscle ICF. In summary, these findings illustrate that activation of AMPK activity with AICAR provokes a significant fall in plasma [K(+)] and suggest a novel mechanism for redistributing K(+) from ECF to ICF.
Zheng
Dan
D
Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, CA 90089-9142, USA.
Perianayagam
Anjana
A
Lee
Donna H
DH
Brannan
M Douglas
MD
Yang
Li E
LE
Tellalian
David
D
Chen
Pei
P
Lemieux
Kathleen
K
Marette
André
A
Youn
Jang H
JH
McDonough
Alicia A
AA
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D015536:Down-Regulation; D004789:Enzyme Activation; D015309:Glucose Clamp Technique; D006706:Homeostasis; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D011188:Potassium / Q000097:blood* / Q000652:urine; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009097:Multienzyme Complexes; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; C031143:AICA ribonucleotide; D011188:Potassium