Cardiac Muscle Cells
Cardiac muscle cells are responsible for providing the power to drive blood through the circulatory system.
Coordination of their activity depends on an electrical stimulus that is regularly initiated at an appropriate rate and reliably conducted through the entire heart.
Mechanical pumping action depends on a robust contraction of the muscle cells that results in repeating cycles of tension development, shortening, and relaxation. In addition, mechanisms to adjust the excitation and contraction characteristics must be available to meet the changing demands of the circulatory system.
[This chapter focuses on these electrical and mechanical properties of cardiac muscle cells that underlie normal heart function.]
All cells have an electrical potential (voltage) across their membranes. Such transmembrane potentials are caused by a separation of electrical charges across the membrane itself. The only way that the transmembrane potential can change is for electrical charges to move across (i.e., current to flow through) the cell membrane.
There are 2 important corollaries to this statement: (1) the rate of change of transmembrane voltage is directly proportional to the net current across the membrane; and (2) transmembrane voltage is stable (i.e., unchanging) only when there is no net current across the membrane.
Unlike a wire, current across cell membranes is not carried by electrons but by the movement of ions through the cell membrane. The 3 ions that are the most important determinants of cardiac transmembrane potentials are sodium (Na+) and calcium (Ca2+), which are more concentrated in the extracellular fluid than they are inside cells, and potassium (K+), which is more concentrated in intracellular than extracellular fluid. (See Appendix B for normal values of many constituents of adult human plasma.) In general, such ions are very insoluble in lipids. Consequently, they cannot pass into or out of a cell through the lipid bilayer of the membrane itself. Instead, these ions cross the membrane only via various protein structures that are embedded in and span across the lipid cell wall. There are 3 general types of such transmembrane protein structures that are involved in ion movement across the cell membrane: (1) ion channels; (2) ion exchangers; and (3) ion pumps. 1 All are very specific for particular ions. For example, a “sodium channel” is a transmembrane protein structure that allows only Na+ ions to pass into or out of a cell according to the net electrochemical forces acting on Na+ ions.
The subsequent discussion concentrates on ion channel operation because ion channels (as opposed to exchangers and pumps) are responsible for the resting membrane potential and for the rapid changes in membrane potential that constitute the cardiac cell action potential. Ion channels are under complex control and can be “opened,” “closed,” or “inactivated.” The net result of the status of membrane channels to a particular ion is commonly referred to as the membrane’s permeability to that ion. For example, “high permeability to sodium” implies that many of the Na+ ion channels are in their open state at that instant. Precise timing of the status of ion channels accounts for the characteristic membrane potential changes that occur when cardiac cells are activated.
Figure 2–1 shows how ion concentration differences can generate an electrical potential across the cell membrane. Consider first, as shown at the top of this figure, a cell that (1) has K+ more concentrated inside the cell than outside, (2) is permeable only to K+ (i.e., only K+ channels are open), and (3) has no initial transmembrane potential. Because of the concentration difference, K+ ions (positive charges) will diffuse out of the cell. Meanwhile, negative charges, such as protein anions, cannot leave the cell because the membrane is impermeable to them. Thus, the K+ efflux will make the cytoplasm at the inside surface of the cell membrane more electrically negative (deficient in positively charged ions) and at the same time make the interstitial fluid just outside the cell membrane more electrically positive (rich in positively charged ions). K+ ion, being positively charged, is attracted to regions of electrical negativity. Therefore, when K+ diffuses out of a cell, it creates an electrical potential across the membrane that tends to attract it back into the cell. There exists one membrane potential called the potassium equilibrium potential at which the electrical forces tending to pull K+ into the cell exactly balance the concentration forces tending to drive K+ out. When the membrane potential has this value, there is no net movement of K+ across the membrane. With the normal concentrations of approximately 145 mM K+ inside cells and 4 mM K+ in the extracellular fluid, the K+ equilibrium potential is roughly −90 mV (more negative inside than outside by nine-hundredths of a volt). 2 A membrane that is permeable only to K+ will inherently and rapidly (essentially instantaneously) develop the potassium equilibrium potential. In addition, membrane potential changes require the movement of so few ions that concentration differences between the intra- and extracellular fluid compartments are not significantly affected by the process.