Inhibition of the α1β1 Isoform of the Na, K-ATPase by 8-methoxycoumestrol Without Positive Inotropic Effect in Human Myocardium-Novel Aspects of Cardiac Glycoside Pharmacology

The Na,K-ATPase (NKA) is necessary for maintaining the resting membrane potential by transporting Na+and K+ions across the cell membrane. Although its 3 isoforms expressed in human heart (α1β1, α2β1, and α3β1) possess similar biochemical properties, their specific functions in human tissues remain unknown. In our search for an isoform-specific agent, which can serve to identify isoform-specific functions, we examined 8-methoxycoumestrol in its ability to inhibit the NKA and to produce inotropism in connection with the possibility to identify the NKA isoform-specific functions.