## Chapter 3: The Hypothetical Myocardial Cell

J. Willis Hurst, MD

[Ventricular Electrocardiography © 1991, 1998 J. Willis Hurst, MD]

### The Depolarization Process

Single cells generate electricity sufficient to be recorded by a very sensitive measuring device. Suppose, for teaching purposes, that the cell and the measuring device could be depicted as in Figure 3.1A. The inside of the cell, which is shown as a three-dimensional structure, is lined with negative (-) electrical charges, while the outside is covered with an equal number of positive (+) electrical charges. A flow of electricity is produced when ions move across the cell membrane. This flow of electricity is from negative to positive, and it produces electrical forces, which can be visualized as vectors and represented as arrows. The measuring device is designed so that it will write an upward defection when the arrow representing an electrical force points toward its positive pole, and a downward line when the arrow points toward its negative pole (Fig. 3.2).

 Figure 3.1 A. hypothetical cell. It should be visualized as being spherical. The reader should imagine that the inside of the cell is lined with negative electrical charges and the outside is covered with positive electrical charges. In this illustration, the positive and negative charges are balanced throughout the cell. Therefore, no electrical forces are produced. B. A sagittal view of the hypothetical cell, showing that the inside of the cell is electrically negative while the outside is electrically positive. Small hypothetical arrows project through the cell membrane. They are used to demonstrate how the electrical forces are balanced. These balanced forces will not influence the measuring device in any way. This is so because the addition of the electrical forces represented by all of the arrows throughout the cell produces a sum that is zero. (See Notes and acknowledgements.)

 Figure 3.2  The measuring device writes an upward deflection when the arrow, representing an electrical force, points toward its positive pole. It writes a downward deflection when the arrow points away from its positive pole. (See Reference 1 and acknowledgement.)

A sagittal view of a hypothetical cell is shown in Figure 3.1B. Several different views of the cell are shown in Figures 3.3 and 3.4, because it is metabolically active and periodically loses and regains its electrical charges.

 Figure 3.3 A. The hypothetical cell is shown in the polarized state. The cell is said to be resting. This implies that the electrical charges inside and outside are arranged in such a manner that no electrical force can be recorded. Accordingly, the measuring device will record a straight line. (see the left side of the illustration). B. The cell is stimulated on the right side, causing the cell membrane to lose its charges on the right side, and permitting the electrical charges on the left side of the cell to gain dominance. The depolarization process spreads from right to left, toward the positive pole of the measuring device, producing an upright deflection on the recording paper. C. The depolarization of the cell has reached the halfway point. The upward deflection has reached its maximum height. D. The depolarization process is about three-quarters complete. The sum of the electrical forces is smaller than when depolarization was at the halfway mark. The forces still produce a line that is above the baseline on the recording paper. E. The depolarization is completed and the deflection returns to the baseline. The cell is said to be in the excited state.
 Figure 3.4 A. The repolarization process (the rebuilding of electrical charges) begins in the area of the hypothetical cell where the depolarization process (the loss of electrical charges) began. Note that the repolarization spreads from right to left but that it produces electrical forces directed from left to right. These forces are directed away from the positive pole of the measuring device. B. This figure shows the repolarization process at the halfway point. The deflection it produces on the recording paper cannot become more negative (downward). C. This figure shows the repolarization process nearing completion. The sum of the arrows is negative, but less so than when repolarization was at the halfway point. D. The repolarization process is complete. All charges have been restored and the cell has returned to the resting state. (See Notes and acknowledgements.

The resting cell, referred to as a polarized cell, is shown in Figure 3.3A. There is no flow of electrical current across the cell wall because each negative charge is balanced by a positive charge. Accordingly, no electrical forces are recorded by the machine.

When the resting cell is stimulated on its right side (Fig. 3.3B), the cell membrane begins the process of losing its electrical charges. The loss of charge takes place in an orderly manner, and the first charges lost are those at the location of the stimulus. The loss of charges can be visualized more vividly if a small arrow is used to represent the relationship of each negative (-) charge to each positive (+) charge on the cell membrane. We must assume that a finite period of time elapses between the loss of one electrical charge and another, and that the measuring device writes an upward line when the electrical force is dominated by arrows that are directed to the left (toward the positive pole).

As a few arrows are removed on the right side of the cell, the arrows located on the left side of the cell dominate the electrical field. This diagram (Fig. 3.3B) represents early depolarization. The process of depolarization proceeds from right to left, producing electrical forces represented by arrows directed from right to left. This results in an upward defection because the arrows are directed toward the positive pole of the measuring device.

Figure 3.3C depicts the depolarization process as it is imagined to be at the halfway point. The measuring device is influenced by all of the arrows on the left side of the cell. The influence on the measuring device is maximum, and the device cannot record a taller line.

Figure 3.3D shows the continuing depolarization of the cell. The process is about three-quarters complete. The sum of the directions of the arrows produces a positive deflection, but one that is less positive than when depolarization was at the halfway mark.

Figure 3.3E illustrates the completion of the depolarization process. This state is sometimes referred to as the excited state. There are no negative (-) charges inside the cell and no positive (+) charges on the surface of the cell. The measuring device is now recording zero (O) because there is no flow of electricity across the cell membrane.

Note: As stated in several places in this book, the model presented here is a clinically useful approximation of the real situation within the heart. At times, the explanation moves beyond the known evidence. When this occurs, every effort has been made to extend the facts in a logical manner.

### The Repolarization Process

The cell in our discussion is metabolically active and programmed to rebuild the electrical charges it has lost. So, after a time delay, the cell membrane begins to restore its charges. It begins to rebuild its charges at the exact spot where it initially lost them. Let us imagine that the time needed for recovery of the charge at each spot on the membrane is the same. When this is true, the spot where the stimulus initiated depolarization will recover its charge first, and the spot at which the charge was lost last will recover its charge last. The time interval between losing and rebuilding the charge will be the same for all parts of the membrane. The repolarization process is depicted in Figure 3.4A through D.

 Figure 3.4

Figure 3.4A depicts the cell actively rebuilding its charges, initially on the right side because it initially lost them there. The amount of time that elapses between the loss and the rebuilding of charge is the same for all parts of the cell membrane. Note that the electrical forces, represented by arrows, now point away from the positive pole of the measuring device and toward its negative pole. This is recorded as a downward deflection.

Figure 3.4B shows the repolarization process at the halfway point. Note that the (repolarization) process itself moves from right to left, but that the measuring device records it as a downward deflection because the electrical forces (represented as arrows) are directed from left to right, away from the positive pole.

Figure 3.4C depicts the repolarization process nearing completion.

Figure 3.4D shows the complete restoration of the electrical charges within and outside the cell membrane. The last area to regain its charges is the spot where the charges were lost last. The cell is now repolarized. It is resting and waiting for another stimulus on its membrane to initiate depolarization once again. Note that in this hypothetical cell, the depolarization process takes place from right to left. This produces electrical forces, represented by arrows, that are directed from right to left. The response of the measuring device is to write an upward deflection. The repolarization process also takes place from right to left, but because the electrical forces, represented as arrows, are directed from left to right, away from the positive pole of the measuring device, it draws a deflection in a downward direction.

### Factors Affecting De- and Repolarization

The diagrams shown in Figures 3.3 and 3.4 depict the depolarization and repolarization processes taking place across the membrane of a hypothetical cell in a simple and orderly manner. At this juncture, the question can be asked: what might alter the orderliness of the depolarization and repolarization of the hypothetical cell? The direction of depolarization can be altered by stimulating the cell at a spot other than that illustrated in Figure 3.3B. This, of course, would alter the direction of the repolarization process. A portion of the cell membrane could also be altered by some intrinsic or extrinsic force such as temperature, pressure, or intrinsic disease. One can conceive of conditions that would influence repolarization but would not alter depolarization. Figure 3.5 illustrates how cooling one side of the cell could alter the sequence of repolarization without significantly altering depolarization.

Figure 3.5A shows a hypothetical cell that has been cooled on its right side. The measuring device records a straight line, indicating a resting cell that is generating zero (0) electrical forces.

 FIGURE 3.5 A. The hypothetical cell has been cooled on the right side. The electrical charges are arranged to show that the cell is resting and no electrical force is generated. This registers a straight line on the recording paper. B. The cell is stimulated on the right side. Because the right side of the cell is cooled, it loses its electrical charges more slowly that it did in Figure 3.3B. Depolarization proceeds from right to left, as it did in Figure 3.3, producing a positive (upright) line on the recording paper. Note, however, that the ascending limb of the deflection is slanted a little more than it was in Figure 3.3C because depolarization occurs more slowly in the cooled portion of the cell. C. The depolarization process is complete. The cell is now in the excited state. The cooling of the right side of the cell did not alter the direction of electrical discharge but it did prolong the ascending limb of the deflection. The descending limb, which represents the uncooled portion of the cell, appears just as it did in Figure 3.3E. D. Repolarization begins on the left side of the cell; as a result of the cooling, it is delayed on the right side. The recovery process proceeds from left to right, creating arrows that are directed from right to left. The arrows are directed toward the positive pole of the measuring device and, because of this, generate a positive (upright) deflection on the recording paper. The repolarization process shown here is at the halfway point. E. This figure illustrates the completion of repolarization The deflection created by the repolarization process lasts longer but is not as tall as that created by the depolarization process. (See Reference 1 and acknowledgement at end of chapter.)

Figure 3.5B shows the cell being stimulated on the right side. The direction of the wave of depolarization is again from right to left, as shown in Figure 3.3, but because of the cooling, the upstroke produced by the measuring device is more sluggish than that shown in Figure 3.3. Accordingly, the measuring device will again record an upward deflection, but one that is slightly more slanted than that shown in Figure 3.3.

Figure 3.5C shows complete depolarization of the cell. The cell is now in an excited state. Cooling of the right side of the cell did not change the direction of the depolarization process, but did slow the initial part of it, as shown by the ascending limb of the deflection wave. It is more slanted than the descending limb, which registers the depolarization of the non-cooled side of the cell.

Figure 3.5D illustrates the early phase of the repolarization process. The coolest part (on the right) is not able to restore its electrical charges as quickly as the uncooled portion of the cell (on the left). Accordingly, the recovery process begins on the left, and proceeds from left to right. Note carefully that this creates electrical forces, represented as arrows, that are directed from right to left. Therefore, as the recovery process moves, it influences the measuring device to write an upright deflection.

Figure 3.5D shows the recovery process at its halfway mark.

Figure 3.5E depicts the completion of the repolarization process. Note that the measuring device records an upright deflection for both depolarization and repolarization. The latter process is slower than the former, and therefore produces a deflection that is longer than, but not as tall as, that produced by depolarization. The number of charges lost and regained is the same, and the area under the depolarization curve is the same as that under the repolarization curve.

The Hypothetical Cell In Three Dimensions

Figures 3.1B through 3.5 have depicted a sagittal view of a hypothetical cell. Obviously, this is a great oversimplification of the true condition. Even a single cell is not flat, but has a spatial configuration. This being true, the depolarization and repolarization processes might be directed upward or downward to the right or left, or from front to back. The heart, which is made up of millions of cells, produces electrical forces that are propagated over the entire surface of the body. The recording device (electrocardiograph machine) and its sampling system (lead system) are used to identify the electrical signals that reach the body surface. The clinician's initial objective is to identify the direction, magnitude, and sense of the electrical forces that are generated by the heart. These electrical forces may be directed upward or downward, to the right or left, or from front to back. This should lead the reader to recall the puzzle of the black box (see Fig. 2.1).

Origin of Cellular Electricity

The origin of animal and plant cellular electricity has intrigued scientists for generations.[2] Denis Noble's The Initiation of the Heartbeat summarizes our current knowledge as it relates to cardiac cells .[3]

Figure 3.6 summarizes the ion pumps in cardiac cells and gives typical values of the various ion concentrations. These values may be used to estimate the electrochemical gradients acting on the various ion species.

 FIGURE 3.6  Ion movements across the cell membrane due to pumps. The typical ion concentration within and outside the cell is shown to the reader's left. (Reprinted by permission of Oxford University Press from Noble D: The Initiation of the Heartbeat. (2nd ed., 1979) Oxford University Press, 1979, p 12.)

Action Potential of the Human Ventricular Myocyte

The electrical activity of individual cells can be measured using specialized techniques. There is a difference in the action potential produced by atrial cells, conduction tissue cells, and ventricular myocytes.[11]

Electrical-Mechanical Myocardial Coupling and Relaxation

An electrical stimulus sets in motion a series of cellular actions that culminate in contraction and relaxation of the myocardial cell. Whereas the precise sequence of events is not known, a great deal of information is available on the subject.[11]

Notes and Acknowledgements

George Burch and Travis Winsor wrote A Primer of Electrocardiography in 1945.[1] The book was very popular and was reprinted five times by Lea & Febiger. The text in the book Ventricular Electrocardiography dealing with depolarization and repolarization as well as Figures 3.1 through 3.5 were created after studying the work of Burch and Winsor. Although the text and figures in Ventricular Electrocardiography are different to those published by Burch and Winsor, I wish to credit them for the basic ideas used to produce them.[1] The use of their information was approved by Lippincott, Williams & Wilkins.

### References

1. Burch G, Winsor T: A Primer of Electrocardiography, 24-31. Philadelphia, Lea & Febiger, 1945.
2. Fishman AP, Richards DW (eds): Circulation of the Blood: Men and Ideas. New York, Oxford University Press, 1964.
3. Noble D: The Initiation of the Heartbeat, ed 2. Oxford, Clarendon Press, 1979, pp 10-13.
4. Isenberg G, Trautwein W: The effect of dihydro-ouabain and lithium ions on the outward current in cardiac Purkinje fibres. Evidence for electrogenicity of active transport. Pflugers Arch 1974;350:41.
5. Baker PF: Transport and metabolism of calcium ions in nerve. Prog Biophys 1972;24:177.
6. Luttgau HC, Niedergerke R: The antagonism between calcium and sodium ions on the frog's heart. J Physiol Lond 1958,143:486.
7. Niedergerke R: Movements of Ca+ in beating ventricles of the frog. J Physiol Lond 1963;167:551.
8. Reuter H, Seitz N: The dependence of calcium efflux from cardiac muscle on temperature and external ion composition. J Physiol Lond 1968; 195:451.
9. Glitsch HL, Reuter H, Scholz H: The effect of internal sodium concentration on calcium fluxes in isolated guinea-pig auricles. J Physiol Lond 1970;209:25.
10. Vaughan-Jones RD: Intracellular chloride activity of quiescent cardiac Purkinje fibres. J Physiol Lond 1977;272:32.
11. Schlant RC, Sonnenblick EH: Normal physiology of the cardiovascular system. In Hurst JW (ed); The Heart, 7th ed, McGraw-Hill, New York, 1990, pp 36-39.

Copyright information: Ventricular Electrocardiography by J. Willis Hurst, MD, was initially published by Gower Medical Publishing in 1991. The rights to the book were then transferred to Mosby Wolfe and in 1996 were returned to the author, Dr. Hurst.

J. Willis Hurst, MD, received his degree from the Medical College of Georgia and served his residency in internal medicine at the same institution. He completed his cardiology fellowship with Dr. Paul White at Massachusetts General Hospital in Boston. Dr. Hurst was Professor and Chairman of the Department of Medicine of Emory University School of Medicine from 1957 to 1986. He received the Gifted Teacher Award and Master Teacher Award of the American College of Cardiology and the Distinguished Teacher Award from the American College of Physicians, and was designated a Master of the American College of Physicians. He served as President of the American Heart Association in 1972 and was given the AHA's Gold Heart and Herrick Awards. Dr. Hurst was Chairman of the Cardiovascular Board of the American College of Physicians for several years and served on the council of the National Heart, Lung, and Blood Institute. He was President Lyndon Johnson's cardiologist for 18 years. He is well known for the book The Heart and many other contributions to the medical literature. Currently, Dr. Hurst is Consultant to the Division of Cardiology of Emory University, and spends his mornings teaching and his afternoons writing.