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 m m at hyperpolarizing V m to 20 m m 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 m m 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.