Ouabain increases myofibrillar Ca2+ sensitivity but does not influence the Ca2+ release in human skinned fibres.
The present study investigated the impact of the Na(+) pump inhibitor ouabain (g-strophanthin) on Ca(2+) sensitivity and Ca(2+) release in human right auricular trabeculae (coronary bypass) and in skinned muscle fibres from left ventricular myocardium (cardiac transplantation, dilated cardiomyopathy). A time-dependent increase in force of contraction was observed in right auricular trabeculae in response to ouabain (100 nM) before the intracellular Ca(2+) transient (fura-2) increased (n=6). In triton X-skinned fibres (no sarcoplasmic reticulum) of human failing myocardium, ouabain (1-100 nM) concentration-dependently increased tension at a free extracellular Ca(2+) concentration of 1 microM and the Hill coefficient of the Ca(2+)-dependent tension development. Ouabain (1-100 nM) did not directly induce a Ca(2+) release out of the sarcoplasmic reticulum, nor did it alter the caffeine (10 mM) induced sarcoplasmic reticulum Ca(2+) release in saponin-skinned fibre preparations in which the sarcoplasmic reticulum had been Ca(2+)-loaded. In conclusion, ouabain increases myofibrillar Ca(2+) sensitivity possibly due to an increase in the cooperativity of the thick and thin myofilaments. This mechanism may additionally contribute to the positive inotropic effect of ouabain.
Hambarchian
Njde
N
Laboratory of Muscle Research and Molecular Cardiology, Department of Internal Medicine III, University of Cologne, Joseph-Stelzmann-Str. 9, D-50924 Cologne, Germany.
Brixius
Klara
K
Lu
Rong
R
Müller-Ehmsen
Jochen
J
Schwinger
Robert H G
RH
D000328:Adult; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009210:Myofibrils / Q000187:drug effects* / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013268:Stimulation, Chemical; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology
D002110:Caffeine; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium