Congestive Heart Failure (Part-05) | Cardiac Glycosides | Mechanism of Action of Cardiac Glycosides

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Digitalis compounds are potent inhibitors of cellular Na+/K+-ATPase. This ion transport system moves sodium ions out of the cell and brings potassium ions into the cell. This transport function is necessary for cell survival because sodium diffusion into the cell and potassium diffusion out of the cell down their concentration gradients would reduce their concentration differences (gradients) across the cell membrane over time. Loss of these ion gradients would lead to cellular depolarization and loss of the negative membrane potential that is required for normal cell function. The Na+/K+-ATPase also plays an active role in the membrane potential. this pump is electrogenic because it transports 3 sodium ions out of the cell for every 2 potassium ions that enter the cell. This can add several negative millivolts to the membrane potential depending on the activity of the pump.

Cardiac myocytes, as well as many other cells, have a Na+-Ca++ exchanger (not an active energy-requiring pump) that is essential for maintaining sodium and calcium homeostasis. The exact mechanism by which these exchanger works is unclear. It is known that calcium and sodium can move in either direction across the sarcolemma. Furthermore, three sodium ions are exchanged for each calcium, therefore an electrogenic potential is generated by this exchanger. The direction of movement of these ions (either inward or outward) depends upon the membrane potential and the chemical gradient for the ions.

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