AMPK and substrate availability regulate creatine transport in cultured cardiomyocytes

Marcus D. Darrabie, Antonio Jose Luis Arciniegas, Rajashree Mishra, Dawn E. Bowles, Danny O. Jacobs, Lucia Santacruz

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Profound alterations in myocellular creatine and phosphocreatine levels are observed during human heart failure. To maintain its intracellular creatine stores, cardiomyocytes depend upon a cell membrane creatine transporter whose regulation is not clearly understood. Creatine transport capacity in the intact heart is modulated by substrate availability, and it is reduced in the failing myocardium, likely adding to the energy imbalance that characterizes heart failure. AMPK, a key regulator of cellular energy homeostasis, acts by switching off energy-consuming pathways in favor of processes that generate energy. Our objective was to determine the effects of substrate availability and AMPK activation on creatine transport in cardiomyocytes. We studied creatine transport in rat neonatal cardiomyocytes and HL-1 cardiac cells expressing the human creatine transporter cultured in the presence of varying creatine concentrations and the AMPK activator 5-aminoimidazole- 4-carboxamide-1-β-D-ribonucleoside (AICAR). Transport was enhanced in cardiomyocytes following incubation in creatine-depleted medium or AICAR. The changes in transport were due to alterations in Vmax that correlated with changes in total and cell surface creatine transporter protein content. Our results suggest a positive role for AMPK in creatine transport modulation for cardiomyocytes in culture.

Original languageEnglish (US)
Pages (from-to)E870-E876
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume300
Issue number5
DOIs
StatePublished - May 1 2011

Keywords

  • Adenosine 5'-monophosphate-activated protein kinase
  • Cardiac energy metabolism
  • Cardiac failure
  • Myocardial creatine content

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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