Inotropic effects of L-lysine in the mammalian heart.
We studied the effects of L-lysine in cardiac preparations of mice and men. Of note, L-lysine increased force of contraction in a concentration- and time-dependent manner in isolated electrically paced left atrium of mouse and in human right atrium. It further increased heart rate and left ventricular pressure in the isolated perfused mouse heart. In isolated adult mouse cardiomyocytes, the contractility as assessed by edge detection was increased as well as the Ca(2+) transients after electrically pacing by field stimulation. However, using the patch clamp technique, no effect of L-lysine on action potential duration from a constant holding potential or on current through L-type calcium channels could be observed. However, L-lysine led to a depolarization of unclamped cells. Furthermore, effects of L-lysine were stereospecific, as they were not elicited by D-lysine. The inotropic effects of L-lysine were not abrogated by additionally applied L-ornithine or L-arginine (known inhibitors of lysine transport). However, L-lysine (5 mM) shifted the concentration-response curve for a positive inotropic effect of 5-hydroxytryptamine (5-HT; serotonin) in atrium of transgenic mice (with cardiac specific overexpression of 5-HT(4) receptors) to higher concentrations. In summary, we describe a novel positive inotropic effect of an essential amino acid, L-lysine, in the mammalian heart. One might speculate that L-lysine treatment under certain conditions could sustain cardiac performance. Moreover, L-lysine is able to block, at least in part, cardiac 5-HT(4) receptors.
Boldt
Andreas
A
Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, 06112 Halle, Germany.
Gergs
Ulrich
U
Frenker
Julia
J
Simm
Andreas
A
Silber
Rolf-Edgar
RE
Klöckner
Udo
U
Neumann
Joachim
J
D000200:Action Potentials; D000368:Aged; D000818:Animals; D016275:Atrial Function / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D002316:Cardiotonic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008239:Lysine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D053580:Muscle Strength / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013237:Stereoisomerism; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure
D002316:Cardiotonic Agents; D008024:Ligands; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D008239:Lysine