Question

Sodium-coupled transport is an important way of moving molecules in and out of the cell. Cardiac cells have a transporter for both Na+ and Ca+2; for every 3 Na+ that come into the cell, 1 Ca+2 is exported out of the cell. Ouabain is a drug that inhibits the Na/K pump. Explain what would happen to Na+, K+ and Ca+2 if ouabain was added to cardiac cells (for simplicity’s sake, consider that the only two transporters involved are the Na/K pump and the Na/Ca cotransporter).

Answer 1

The sodium potassium ATPase pump will transport 3 sodium ions out of the cell and two potassium ions inside the cell. There are two conformations E1 and E2 in the functioning of Na+/K+ ATPase pump. There is binding of sodium ions and ATP in E1 conformation to the Na+/K+ ATPase pump. ATP is then hydrolyzed and ADP is removed while Pi remains attached. This alters the conformation of the pump to E2 phase. In this phase, the three sodium ions dissociate and are released to the extracellular side. The pump then binds to 2 K+ ions in extracellular side. There is hydrolysis of the bound Pi, which results in formation of E1 conformation of the pump. Quabain, a cardiac glycoside can bind to protein residues inside the pump, just prior to binding of K+. Thus, Quabain prevents the transition of E1 phase from E2 phase, thereby inhibiting the Na+/K+ pump in cardiac cells. Potassium ions will therefore decrease in the cells while cytoplasmic sodium levels increase. This inhibitory effect will affect the cardiac cells indirectly. There will be indirect effect on ionotrophy (contractibility) of these cells. Quabain will increase the cytoplasmic sodium levels. As a result, there is effect on sodium-calcium exchanger. This exchanger is involved in transport of sodium into the cells and calcium out of the cells. As sodium levels increase in cytoplasm, the exchanger will not transport any more sodium into the cells. This will result, in increased levels of calcium in the cytoplasm of cardiac cells as well. Calcium is a second messenger and its increased levels, will increase muscle contraction. Calcium accumulates in sarcoplasmic reticulum and is released during depolarization. As a result, there is increased force of muscle contraction. Thus, Quabain increases the contractibility or ionotrophy of cardiac muscle cells.