AMPK and substrate availability regulate creatine transport in cultured cardiomyocytes.

Journal Article

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 V(max) 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.

Full Text

Duke Authors

Cited Authors

  • Darrabie, MD; Arciniegas, AJL; Mishra, R; Bowles, DE; Jacobs, DO; Santacruz, L

Published Date

  • May 2011

Published In

Volume / Issue

  • 300 / 5

Start / End Page

  • E870 - E876

PubMed ID

  • 21364119

Electronic International Standard Serial Number (EISSN)

  • 1522-1555

Digital Object Identifier (DOI)

  • 10.1152/ajpendo.00554.2010

Language

  • eng

Conference Location

  • United States