L-Arginine currents in rat cardiac ventricular myocytes.
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 Na(2+), K(2+), Ca(2+) and Mg(2+). The process displayed saturation and membrane potential (V(m))-dependent kinetics, with a K(0.5) for l-Arg that increased from 5 mm at hyperpolarizing V(m) 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 y(2+) 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.
Peluffo
R Daniel
RD
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. peluffrd@umdnj.edu
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005033:Ethylmaleimide / Q000494:pharmacology; D045604:Extracellular Fluid / Q000378:metabolism; D006706:Homeostasis; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D051381:Rats; D016276:Ventricular Function / Q000187:drug effects*
D009569:Nitric Oxide; D001120:Arginine; D005033:Ethylmaleimide