Sodium-Calcium Exchange in Cardiac Cells
Intracellular calcium concentrations in both cardiac and vascular smooth muscle cells range from 10-7 to 10-5 M. Extracellular concentration of calcium is about 2 × 10-3 M (2 mM). Therefore, there is a chemical gradient for calcium to diffuse into the cell. Because cells have a negative resting membrane potential (about -90 mV in a cardiac myocyte), there is also an electrical force driving calcium into the cell. However, except during action potentials when the cell membrane permeability to calcium increases, there is little leakage of calcium into the cell. The calcium that enters the cell during action potentials (e.g., during depolarization of pacemaker and non-pacemaker cardiac cells) must be removed from the cell otherwise an accumulation of calcium would lead to cellular dysfunction.
We also know that an increase in intracellular sodium concentration leads to an increase in intracellular calcium concentration through this exchange. This has important physiological implications. One example of this occurring is when the activity of the Na+/K+-ATPase pump is decreased. This energy requiring, ATP-dependent pump transports sodium out of the cell and potassium into the cell. When the activity of this pump is reduced, for example, by cellular hypoxia (which causes ATP levels to fall) or by chemical inhibitors of this pump such as digitalis, then intracellular Na+ concentrations increase. One way to envision how this affects Ca++ exchange is that the increased intracellular Na+ reduces the concentration gradient of Na+ across the sarcolemma, which reduces the inward movement of Na+ down its concentration gradient via the exchanger. This, in turn, reduces the outward movement and exchange of Ca++, which leads to an accumulation of intracellular calcium. This is the mechanism by which digitalis increases cardiac inotropy. Under hypoxic conditions, the enhanced calcium concentrations cannot increase inotropy because of the lack of ATP; however, the increased intracellular calcium (termed calcium overload) can damage mitochondria and alter cellular function.