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J Physiol Volume 580, Number 3, 925-936, May 1, 2007 DOI: 10.1113/jphysiol.2006.125054
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CARDIOVASCULAR

L-Arginine currents in rat cardiac ventricular myocytes

R. Daniel Peluffo1

1 Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07101, USA

L-Arginine (L-Arg) is a basic amino acid that plays a central role in the biosynthesis of nitric oxide, creatine, agmantine, polyamines, proline and glutamate. Most tissues, including myocardium, must import L-Arg from the circulation to ensure adequate intracellular levels of this amino acid. This study reports novel L-Arg-activated inward currents in whole-cell voltage-clamped rat ventricular cardiomyocytes. Ion-substitution experiments identified extracellular L-Arg as the charge-carrying cationic species responsible for these currents, which, thus, represent L-Arg import into cardiac myocytes. This result was independently confirmed by an increase in myocyte nitric oxide production upon extracellular application of L-Arg. The inward movement of Arg molecules was found to be passive and independent of Na2+, K2+, Ca2+ and Mg2+. The process displayed saturation and membrane potential (Vm)-dependent kinetics, with a K0.5 for L-Arg that increased from 5 mM at hyperpolarizing Vm to 20 mM at +40 mV. L-Lysine and L-ornithine but not D-Arg produced currents with characteristics similar to that activated by L-Arg indicating that the transport process is stereospecific for cationic L-amino acids. L-Arg current was fully blocked after brief incubation with 0.2 mM N-ethylmaleimide. These features suggest that the activity of the low-affinity, high-capacity CAT-2A member of the y2+ family of transporters is responsible for L-Arg currents in acutely isolated cardiomyocytes. Regardless of the mechanism, we hypothesize that a low-affinity arginine transport process in heart, by ensuring substrate availability for sustained NO production, might play a cardio-protective role during catabolic states known to increase Arg plasma levels severalfold.

(Received 16 November 2006; accepted after revision 13 February 2007; first published online 15 February 2007)
Corresponding author R. D. Peluffo: Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, PO Box 1709, Newark, NJ 07101-1709, USA.  Email: peluffrd{at}umdnj.edu


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C. V. Remillard and J. X.-J. Yuan
Cardiac L-arginine transport: the CAT is back
J. Physiol., May 1, 2007; 580(3): 699 - 700.
[Full Text] [PDF]




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