Cellular mechanism of action of cardiac glycosides.
It has long been known that cardiac glycosides can inhibit the membrane sodium-potassium (Na+-K+) pump, raising intracellular Na+. However, at clinical concentrations of cardiac glycosides, a change in intracellular Na+ that correlates with a change in cardiac contraction has been very difficult to demonstrate. The recent use of Na+-sensitive microelectrodes in the experimental laboratory has made intracellular Na+ measurements possible. A doubling of contraction strength in vitro is associated with a change of only approximately 1 mM intracellular Na+. Another membrane transport system, the Na+-Ca2+ exchange system, exchanges extracellular Na+ for intracellular Ca2+. If this system is responsible for regulating intracellular Ca2+, then it would be very sensitive to the transmembrane Na+ concentration gradient. This influence of intracellular Na+ on Na+-Ca2+ exchange is though to be the cellular basis of the positive inotropic action of digitalis. However, a number of issues remain unresolved, such as the extent of Na+-K+ pump inhibition by the level of cardiac glycoside achieved clinically.
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D000200:Action Potentials / Q000187:drug effects; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002301:Cardiac Glycosides / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D004071:Digitalis Glycosides / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008839:Microelectrodes; D009124:Muscle Proteins / Q000378:metabolism / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D012964:Sodium / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D002301:Cardiac Glycosides; D004071:Digitalis Glycosides; D007473:Ion Channels; D009124:Muscle Proteins; D012964:Sodium; D011188:Potassium; D002118:Calcium