Figure 18-1 illustrates the measurement of the RMP through the placement of one microelectrode inside the cell and another outside the cell. A wire from each microelectrode is connected to a voltmeter, which measures the electrical potential difference across the membrane at about −90 mV.

Figure 18-1 Measurement of the RMP. The recording electrode is inside and the reference electrode is outside of the cell, measuring a potential difference (voltage) of −90 mV.

The main ions involved in generating the RMP are sodium (Na⁺), potassium (K⁺), calcium (Ca⁺⁺), and large protein anions (negatively charged ions). As with all other cells in the body, K⁺ ion concentration inside the cardiac cell is much greater than outside the cell (about 151 mEq/L vs. 4 mEq/L).² The opposite is true for Na⁺ and Ca⁺⁺ ions; [Na⁺] is about 144 mEq/L outside the cell and about 7 mEq/L inside the cell, and [Ca⁺⁺] is 5 mEq/L outside the cell and less than 1 mEq/L inside the cell.

The resting cardiac cell membrane is fairly permeable to K⁺ ions but only slightly permeable to Na⁺ and Ca⁺⁺ ions. The permeability of the membrane to K⁺ allows potassium to diffuse out of the cell, down its high concentration gradient (Figure 18-2). Large, negatively charged protein ions and molecules cannot diffuse outward with K⁺ because the cell membrane is completely impermeable to them. Thus, as potassium leaves, an increasingly negative intracellular charge develops; this represents an electrostatic force that slows and eventually stops the outward diffusion of K⁺. The equilibrium between the outward diffusion force of K⁺ and the cell’s electrostatic attractive force is largely responsible for the cardiac cell RMP, altered only slightly by Na⁺ ion diffusion dynamics, as explained next.

Figure 18-2 Potassium equilibrium potential. The outward diffusion force of potassium is in equilibrium with the inward electrostatic attraction exerted by nondiffusible protein anions.

Although the cardiac cell membrane is highly impermeable to Na⁺, small amounts of this ion diffuse through leak channels into the cell because of its extremely high diffusion gradient (Figure 18-3).¹ This diffusion alters the potassium-driven membrane potential, causing it to be slightly less negative (closer to 0) than it would be otherwise. The Na⁺-K⁺ exchange pump in the cell membrane counteracts Na⁺ leakage into the cell by actively pumping it out while pumping potassium back in. Three Na⁺ ions are pumped out of the cell for every two K⁺ ions pumped back in, adding to the electronegativity of the intracellular environment (see Figure 18-3). In the end, the RMP is the result of the complex interactions between (1) chemical diffusion forces, (2) electrostatic attractive forces, and (3) the Na⁺-K⁺ exchange pump.

Figure 18-3 Generation of the RMP. The potassium equilibrium potential is altered by a small influx of Na⁺ ions through leak channels and the unequal pumping of Na⁺ and K⁺ ions.

CONCEPT QUESTION 18-1

Explain how high extracellular K⁺ concentration affects the RMP and heart muscle excitability.

Ion Channels and Gates

Sodium and Potassium Channels

The permeability of the myocardial cell membrane to Na⁺ and K⁺ ions is mainly controlled by voltage-gated ion channels in the membrane (Figure 18-4). These channels are formed by large protein molecules and are specific for each ion. Gatelike structures called gating proteins control these channels. Gating proteins are voltage sensitive, opening and closing in response to changes in the membrane potential. Changes in membrane potential alter the shape of the protein molecule, which opens or closes the channel gates² (i.e., the membrane’s permeability to K⁺ and Na⁺ is voltage dependent).

As shown in Figure 18-4, K⁺ and Na⁺ channel activation gates are closed at the cardiac cell’s RMP of −90 mV. Although both of these channels are closed, some K⁺ and Na⁺ ions diffuse across the membrane through leak channels because of their high diffusion gradients.

Calcium Channels

In addition to the Na⁺ and K⁺ channels, cardiac fibers have numerous calcium ion channels. These channels are similar to Na⁺ channels in that they have activation and inactivation gates. However, calcium channel gates respond 10 to 20 times more slowly than sodium channel gates to changes in membrane potential.¹ Calcium channels are therefore called slow channels, whereas sodium channels are called fast channels. Although they mainly transmit Ca⁺⁺ ions, calcium channels also permit the passage of some Na⁺ ions. The responses of sodium, potassium, and calcium channels to changes in their membrane potentials bring about an event known as the action potential. The action potential is an electrical event ultimately leading to the mechanical event of muscle fiber contraction.

Action Potential

Cardiac muscle fiber depolarization occurs when the fiber RMP of −90 mV abruptly changes to 0 mV. Repolarization occurs when the RMP is again established at −90 mV. The action potential is a real-time recording of the moment-to-moment changes in the membrane potential as the cardiac fiber depolarizes and repolarizes. This recording plots voltage against time on specially designed graph paper or a monitoring screen. Figure 18-5 illustrates the action potential of a single ventricular muscle fiber. The different phases of the action potential (0 to 4) are created by Na⁺, K⁺, and Ca⁺⁺ movement in and out of the cell.

Depolarization: Phase 0

The action potential of a ventricular muscle fiber (see Figure 18-5) is normally initiated by an electrical impulse originating from the sinoatrial (SA) node in the right atrium. The impulse changes the RMP to a less negative value that begins to open some of the fast sodium channel activation gates. Increased influx of sodium makes the fiber’s membrane potential even less negative, causing more activation gates to swing open. When the membrane potential reaches a critical level called the threshold potential (TP), all activation gates open instantaneously; this brings about an explosive influx of Na⁺, which instantaneously depolarizes the cell membrane and generates the upstroke (phase 0) of the action potential (see Figure 18-5).

Two forces cause Na⁺ ions to enter the cell during phase 0 of the action potential: (1) an electrostatic attraction created by the negative intracellular environment and (2) a high chemical diffusion force favoring movement of sodium into the cell (Figure 18-6, A). When the membrane potential reaches 0 mV, Na⁺ continues to enter the cell because a strong diffusion gradient is still present (see Figure 18-6, B and C). Consequently, the cell membrane’s polarity reverses (the membrane potential peaks at about +30 mV), creating the overshoot of the action potential (see Figures 18-5 and 18-6, D).

Figure 18-6 **A-E,** Sodium channel gating activity generating the upstroke (phase 0) of the action potential. See text for explanation.

The rapid change in membrane potential from −90 mV to +30 mV causes the voltage-sensitive inactivation gates of the sodium channel to swing closed rapidly, stopping the influx of sodium (see Figure 18-6, E). These inactivation gates close only a few ten-thousandths of a second after the activation gates open—about the time the upstroke of the action potential reaches 0 mV, on its way to +30 mV.¹ The inactivation gates do not reopen until the original RMP is restored; thus, the heart muscle fiber first must repolarize before it can respond to another depolarizing stimulus. That is, the heart muscle fiber is refractory to depolarizing stimuli from phase 0 through the end of phase 3 of the action potential (see Figure 18-5).

Some cardiac drugs inhibit the opening of fast sodium channels, decreasing the membrane’s susceptibility to depolarization. Such drugs are used when the membrane depolarizes too readily, disturbing the cardiac rhythm. Sodium channel–inhibiting drugs are classified as antiarrhythmic drugs (e.g., quinidine, amiodarone, and lidocaine).

CONCEPT QUESTION 18-2

Referring to Figure 18-5, do antiarrhythmic drugs raise (bring closer to 0) or lower the TP (assuming the RMP remains constant at −90 mV)?

Plateau: Phases 1 and 2

Immediately after the upstroke of the action potential (phase 0), a very small, limited downstroke occurs (phase 1) just before the plateau. This brief decline in intracellular positivity reflects the sudden opening of potassium channel gates and outflow of K⁺ from the cell (Figure 18-7, phase 1). Almost simultaneously, slow calcium channel activation gates finally swing open, allowing Ca⁺⁺ and a small amount of Na⁺ to enter the cell (see Figure 18-7, phase 2). This inflow of positive charges (carried by Ca⁺⁺ and Na⁺) is counterbalanced by an equal outflow of positive charges (carried by K⁺). A membrane potential of about 0 mV is thus briefly maintained, creating the action potential’s plateau (see Figure 18-7, phase 2).

Figure 18-7 Na⁺, K⁺, and Ca⁺⁺ movements that generate the ventricular muscle fiber action potential.

Compared with the depolarization phase (see Figure 18-7, phase 0), which lasts only a few ten-thousandths of a second, the plateau phase lasts for about 0.2 to 0.3 second.¹ Therefore, cardiac muscle contraction also lasts for this relatively long time, a property of cardiac muscle that enhances its pumping effectiveness.

Ca⁺⁺ ions entering the myocardial fiber during the plateau phase participate in the excitation-contraction coupling between actin and myosin fibers, as described in Chapter 17. Some drugs, such as digitalis, increase the intracellular level of Ca⁺⁺, which enhances myocardial contractility during this phase of the action potential. Drugs that increase contractility are called inotropic drugs.

The equilibrium between Ca⁺⁺ inflow and K⁺ outflow during the plateau occurs in ventricular but not in atrial myocardial fibers. K⁺ outflow exceeds Ca⁺⁺ inflow in atrial fibers, preventing the development of a plateau.¹

Repolarization: Phase 3

The outflow of K⁺ ions gradually increases throughout the action potential plateau. The plateau phase ends when Ca⁺⁺ inactivation gates close, stopping Ca⁺⁺ inflow (see Figure 18-7, phase 3). The membrane is now highly permeable to only K⁺ ions. Intracellular negativity is rapidly restored to the resting level as K⁺ explosively rushes out of the cell, down its high diffusion gradient. After repolarization is complete and the RMP is restored, excess Na⁺ that entered the cell during phases 0 and 2 is pumped out by the Na⁺-K⁺ exchange pump. At the same time, K⁺ that exited the cell during phases 2 and 3 is pumped back into the cell, restoring the original Na⁺ and K⁺ concentrations inside and outside the cell (see Figure 18-7, phase 4). The muscle fiber is then ready to accept another depolarizing stimulus. Box 18-1 summarizes the events causing the action potential.

Action Potential Propagation

Depolarization of a specific point on a cardiac fiber membrane opens sodium channels at that point. Positive electrical charges carried by the inflow of Na⁺ ions decrease the intracellular negativity immediately adjacent to the point of entry, bringing these areas to their threshold potentials. Sodium channels in these areas immediately open, allowing more Na⁺ to rush in. This new incoming Na⁺ brings areas farther along the fiber to their threshold potentials, and so on, instantaneously spreading the action potential along the fiber. The inflow of positively charged Na⁺ ions leaves a relatively negative charge on the outside fiber surface. Thus, the action potential spreads as a wave of electronegativity across the surface of the depolarizing fiber membrane (Figure 18-8). This electronegative wave is called an electrical impulse, which can be detected on the body’s surface with a special instrument called an electrocardiograph.

Figure 18-8 Propagation of the action potential along the cardiac fiber. (From Thibodeau GA, Patton KT: *Anatomy & physiology,* ed 3, St Louis, 1996, Mosby.)

In summary, a depolarizing impulse spreads over the myocardial surface and deep into the fiber through the T-tubules (see Chapter 17). This impulse ultimately opens calcium channels, allowing Ca⁺⁺ to enter the fiber and catalyze the excitation-contraction coupling of actin and myosin myofibrils. The mechanical muscle contraction event occurs only a few milliseconds after muscle fiber depolarization.

Effects of Drugs and Extracellular Ion Concentration on the Action Potential

Extracellular Ions

Potassium

An excess of potassium ions (hyperkalemia) in the extracellular fluid surrounding cardiac fibers decreases the heart rate and stroke volume. Severe hyperkalemia causes heart block, or the inability of cardiac fibers to conduct action potentials through the heart. The mechanism by which hyperkalemia causes these effects is illustrated in Figure 18-9.

As mentioned previously, K⁺ diffusion out of the cell down its concentration gradient is primarily responsible for generating RMP (see Figure 18-2). High extracellular [K⁺] diminishes the outward diffusion gradient of K⁺. As a result, a smaller degree of intracellular electronegativity develops when potassium diffuses out of the cell. This means that the RMP across the cell membrane is less negative (closer to 0) and closer to the TP (see Figure 18-9). Hyperkalemia thus has a depolarizing influence on the membrane, making it more excitable (easier to depolarize). Excitability is defined as the difference between the RMP and the TP; the less the difference, the more excitable the membrane.³

Besides making the RMP less electronegative, hyperkalemia reduces the amplitude (strength) of the action potential, decreasing its rate of conduction along muscle fibers, which explains why hyperkalemia decreases the heart rate. The decreased action potential amplitude also reduces the amount of Ca⁺⁺ that enters the muscle fiber during depolarization, which decreases ventricular contraction force and stroke volume. Severe hyperkalemia may depolarize the membrane to the extent that its resting potential is less (closer to 0) than its TP.³ In this case, the muscle fiber is unable to repolarize after a single action potential and is no longer excitable (i.e., the fiber is in a continual state of depolarization). This leads to cardiac muscle paralysis and is why hyperkalemia may cause heart block.

Conversely, hypokalemia increases the diffusion gradient for K⁺ movement out of the cell, creating a greater intracellular electronegativity than normal. As a result, the RMP is lower than normal, hyperpolarizing the membrane (see Figure 18-9); this makes the membrane less excitable or less sensitive to depolarizing stimuli. In severe hypokalemia, the heart muscle may fail to depolarize, resulting in flaccid paralysis (cardiac arrest).³ Hypokalemia may decrease the heart rate because a longer time is required for the membrane to depolarize to its threshold level. The muscle contraction force is not affected in this instance because adequate amounts of Ca⁺⁺ enter the cell during the action potential.

Calcium

Ca⁺⁺ entry into cardiac fibers during the plateau phase of the action potential is essential for muscle contraction (see Chapter 17). Generally, the heart muscle contractile force is directly related to extracellular [Ca⁺⁺].

Calcium ions affect membrane excitability by changing the TP rather than the RMP. This phenomenon is explained by the effect of Ca⁺⁺ on sodium channel activation. When extracellular [Ca⁺⁺] is low (hypocalcemia), an extremely small amount of membrane depolarization above the resting potential opens the sodium channels. In other words, hypocalcemia brings the threshold at which Na⁺ activation gates open closer to the RMP. For example, rather than opening at a normal TP of −65 mV, Na⁺ gates open at −75 mV, a value much closer to the −90-mV RMP (Figure 18-10). Thus, hypocalcemia increases heart muscle excitability, causing an effect similar to hyperkalemia. Apparently, Ca⁺⁺ ions bind to sodium channel protein molecules, increasing the amount of membrane depolarization that must occur to open the gate. Therefore, low extracellular [Ca⁺⁺] allows the gate to open with an extremely small degree of membrane depolarization.¹

Figure 18-10 Effect of extracellular calcium concentration on TP and membrane excitability.

Conversely, hypercalcemia decreases membrane excitability because it raises the TP, requiring a greater amount of membrane depolarization to open the Na⁺ gates (see Figure 18-10). Because of its direct effect on the muscle contractile process, extremely high [Ca⁺⁺] can cause the heart to develop repetitive, spastic contractions. Because blood [Ca⁺⁺] is regulated within extremely narrow ranges, calcium-induced cardiac abnormalities are rarely a clinical concern.¹ However, administering Ca⁺⁺ to treat severe hyperkalemia may be clinically beneficial because doing so counteracts the effect of hyperkalemia on membrane excitability.³

Sodium

Changes in extracellular [Na⁺] have little effect on the RMP of cardiac muscle because the membrane is highly impermeable to Na⁺. Therefore, abnormal depolarization is rarely related to abnormal extracellular [Na⁺].

Drugs Affecting the Action Potential

Catecholamines

Catecholamines are compounds with chemical structures similar to epinephrine and norepinephrine. Such drugs increase the influx of Ca⁺⁺ into the myocardial cell during the plateau phase of the action potential. Catecholamines activate beta receptors in the cardiac cell membrane, bringing about a series of chemical events that increase intracellular levels of cyclic adenosine monophosphate (cAMP). cAMP enhances activation of the slow calcium channels, augmenting the influx of Ca⁺⁺ ions. This is the main mechanism by which catecholamine drugs increase cardiac muscle contractility.² Sympathetic nervous activity raises heart muscle contractility by the same mechanism because it raises adrenal secretion of epinephrine into the circulation.

Beta-blocking drugs such as propranolol compete with catecholamines for beta-receptor sites and thus reduce cardiac contractility and the heart rate. These drugs are sometimes given to control abnormally high heart rates or to reduce cardiac work and oxygen consumption. Beta blockers also decrease vascular smooth muscle tone and are sometimes used to treat high blood pressure.

As mentioned previously, digitalis increases contractility by increasing calcium stores in the cardiac fiber. Digitalis is sometimes given to patients with congestive heart failure to improve contractility and pumping effectiveness.

Calcium Channel Blockers

As the name implies, calcium channel–blocking drugs block the calcium channel, decreasing the entry of Ca⁺⁺ into the cell during muscle contraction (plateau phase of the action potential). These drugs are also known as slow channel blockers or calcium antagonists. As expected, their main effect is to decrease the muscle’s contractile force, reducing the heart’s stroke volume. This effect may be beneficial in coronary artery disease, in which the blood and oxygen supply to the myocardium is impaired. Decreased contractility requires less oxygen consumption by the heart muscle. Calcium antagonists also decrease smooth vascular muscle contraction and are widely used as coronary vasodilators to improve coronary circulation. They are also used to treat systemic hypertension. Examples of these drugs include verapamil, nifedipine, diltiazem, and nicardipine.

Rhythmic Excitation of the Heart

Automatic Rhythmicity of the Cardiac Fibers

Although sympathetic and parasympathetic nerves innervate the heart, cardiac function does not require intact nervous pathways. A clinical example is a patient with a cardiac transplant whose heart is completely denervated but functions normally and adapts to stress appropriately. The heart can continue to beat even when removed from the body if it is appropriately nourished by artificial means. All cardiac tissue has properties of (1) automaticity (the ability to depolarize spontaneously), (2) rhythmicity (the ability to depolarize spontaneously in a repetitive manner), (3) excitability (the inclination to depolarize spontaneously), and (4) contractility (the ability to shorten muscle fibers).

Pacemaker Function of the Sinus Node

The cardiac tissue that generates the greatest frequency of impulses is the SA node in the right atrium because it is the most excitable tissue; this makes the SA node the heart’s natural pacemaker. Although every other cardiac cell is a potential pacemaker, none can initiate depolarization because the SA node impulse depolarizes them first before they can reach their threshold potentials.

CONCEPT QUESTION 18-3

What happens if the SA node fails to generate any impulses in an otherwise healthy heart?

The RMP of sinus node fibers is only about −55 mV compared with −90 mV of ventricular fibers (Figure 18-11).¹ Sinus node tissue is naturally leakier than ventricular fibers to sodium ions; hence, its intracellular environment is less negative. In addition, the RMP of the SA node is closer to its TP than other heart muscle; its threshold is about −40 mV, creating an RMP-TP difference of about 15 mV. In contrast, ventricular muscle RMP and TP are about −90 mV and −65 mV, for an RMP-TP difference of about 25 mV. Thus, the ventricles require more time than the SA node to reach the TP (see Figure 18-11). Hence, the SA node sets the pace and suppresses all other cardiac cell pacemaker tendencies.

Figure 18-11 Pacemaker function of the SA node. Because the RMP of the SA node is closer to its TP, its fibers depolarize sooner than ventricular fibers. The SA node is the dominant pacemaker because its impulses depolarize other pacemaker cells before they can reach their thresholds.

Sinus Node Self-Excitation

Figure 18-11 illustrates the sinus node’s gradually rising RMP caused by the slow leak of Na⁺ into the cell. When its threshold of −40 mV is reached, the SA node fires (depolarizes), initiating an impulse that spreads to all heart muscle over the specialized conduction system. As soon as repolarization is achieved, RMP immediately begins to decay again toward the TP, causing the cycle to repeat itself at regular intervals. The heart rate pattern established by the SA node is known as sinus rhythm and is normally about 70 to 80 beats per minute.¹

Ectopic Beats

If the sinus node fails to discharge its impulses, the next most excitable myocardial cell spontaneously depolarizes and initiates the heartbeat at a lower rate. Alternatively, if the sinus node is functioning properly but another area in the heart muscle becomes irritated (e.g., hypoxic) and develops an abnormal RMP, it may depolarize sooner than the sinus node and initiate a premature heartbeat. Both of these situations represent ectopic beats. The term ectopic means the impulse originated from an area outside of the sinus node. The point from which such an impulse originates is known as an ectopic focus. Ectopic foci may become ectopic pacemakers if (1) they become more excitable or irritable than the SA fibers, (2) the SA node fails to initiate the impulse, or (3) conduction pathways between ectopic foci and the SA node become blocked.

Premature Beat

A premature beat occurs early between otherwise evenly spaced, sinus-generated beats. A premature beat is evidence that an ectopic focus has fired. In other words, an ectopic focus can initiate a beat prematurely only if it depolarizes more rapidly than the SA node. Factors that may produce such premature beats include (1) local areas of tissue hypoxia (ischemia); (2) mechanical irritation produced by calcified plaque in a diseased heart; and (3) toxic irritation caused by nicotine, caffeine, or other drugs.¹ All of these factors cause the heart muscle to become more excitable and more susceptible to depolarization.

CONCEPT QUESTION 18-4

Does an atrial ectopic focus acting as the heart’s pacemaker have a greater firing rate than the SA node?

Downward Displacement of the Pacemaker

All cells in the cardiac conduction system are potential pacemakers, but not all have the same spontaneous depolarization rate. Lower order pacemakers (pacemakers with spontaneous depolarization rates lower than the SA node) normally cannot pace the heartbeat because the rapidly firing SA node suppresses them. If the SA node suddenly stops firing, lower order pacemaker cells begin to fire after a few seconds’ pause. This brief pause is known as overdrive suppression. When lower order pacemaker cells are driven at high frequencies, their automaticity is temporarily depressed. These pacemaker cells remain inactive for a few seconds after the SA node stops firing and then establish a new, lower firing rate. The takeover of pacemaking activity by lower order pacemakers is known as downward displacement of the pacemaker.

After the SA node, the atrioventricular (AV) nodal fibers have the next highest spontaneous depolarization rate. If not stimulated from some outside source, AV fibers fire at a rate of 40 to 60 times per minute. If AV impulses fail to reach the ventricles after several seconds, the Purkinje fibers begin to fire at a rate of 15 to 40 times per minute.¹ These rates contrast with the intrinsic SA nodal rate of 70 to 80 beats per minute.

Lower order pacemakers not only fire at lower rates, they also tend to be more unreliable than the SA node. Ventricular pacemakers are especially unstable in this regard. If impulses from atria are totally blocked, the Purkinje cells may pause for 30 seconds before establishing a rate of 15 to 40 beats per minute. During this pause, there is no cardiac output, and the person may faint from lack of blood flow to the brain. This delayed ventricular takeover of the heartbeat is known as Stokes-Adams syndrome.¹

Transmission of Impulses through the Heart

Atrial Transmission

The cardiac conduction system anatomy is discussed in Chapter 17. From the SA node, the depolarizing impulse spreads rapidly over atrial muscle to the AV node. The impulse is preferentially conducted along three specialized internodal pathways that eventually converge at the AV node.¹ One of these pathways, Bachmann’s bundle, conducts SA nodal impulses directly to the left atrium (Figure 18-12). The impulse velocity over these specialized conductive pathways is about 1 m per second compared with 0.3 m per second over other atrial muscle.¹

Figure 18-12 The heart’s specialized conductive tissues.

Clinical Focus 18-1 Clinical Benefits of Using Drugs to Alter Electrophysiological Events

Drugs that alter electrophysiological events in the heart often benefit patients with atherosclerotic heart disease. In this disease, abnormal fatty substances (atheroma) build up under the endothelium of coronary arteries, partially occluding them. As a result, blood flow may not meet the heart’s oxygen requirements, creating myocardial ischemia and its associated pain, angina pectoris. Lack of oxygen causes myocardial irritability, increasing the chances that tachycardia and dangerous ectopic rhythms may develop. Complete lack of oxygen for a sustained period may cause a myocardial infarction (MI), an area of dead heart tissue, especially if myocardial work increases. Antianginal and antiarrhythmic drugs are beneficial in these patients.

Antiarrhythmic drugs decrease the irritability of ectopic foci, allowing normal SA nodal pacing. In this group of drugs, lidocaine (Xylocaine) and amiodarone (Cordarone) block Na⁺ channels, decreasing the membrane’s tendency to depolarize. Beta-receptor blockers such as carvedilol (Coreg) and bisoprolol (Zebeta) depress the myocardium’s automaticity, decreasing tachycardia and myocardial work. Calcium channel blockers such as amlodipine (Norvasc) and diltiazem (Cardizem) inhibit slow channel influx of Ca⁺⁺ in the SA node and other myocardial cells. This inhibition depresses atrial automaticity, slows AV conduction velocity, and decreases myocardial contractility.

Calcium channel blockers also inhibit Ca⁺⁺ entry into vascular smooth muscle, dilating coronary and systemic vessels. Systemic vascular resistance is lowered, allowing the heart to sustain an adequate cardiac output despite its reduced contractility. By decreasing myocardial contractility, Ca⁺⁺ channel blockers reduce the heart’s oxygen requirements, decreasing the chances for developing an MI. Because of their coronary vasodilating properties, these drugs improve blood and oxygen supply to the myocardium, further decreasing the potential for MI. Calcium channel blockers are thus also classified as antiarrhythmic and antianginal drugs. Other antianginal drugs include nitrates, such as nitroglycerin. These drugs dilate coronary arteries by releasing nitric oxide in vascular smooth muscle.

CONCEPT QUESTION 18-5

Extremely rapid heart rates decrease the ventricular filling time. Besides being more rapid, how does this change the character of the pulse palpated at the radial artery?

Atrioventricular Conduction

If the SA nodal impulse was immediately conducted into the ventricles, ventricular contraction would begin before the atria have time to fill them with blood. The AV node delays impulse conduction enough to allow adequate ventricular filling time.

The AV node is located in the septal wall of the right atrium, just behind the tricuspid valve. The SA node impulse travels across atrial muscle to the AV node in about 0.03 second; however, the impulse does not emerge from the AV node for another 0.13 second.¹ About one fourth of the total delay occurs in the transitional (junctional) fibers (extremely small fibers connecting atrial muscle to nodal fibers). The conduction velocity in junctional fibers is about one twelfth of the velocity in normal cardiac muscle.¹ Nodal resistance to conduction is not quite as high as junctional resistance but is still greater than that for other heart muscle.

The AV bundle, also known as the bundle of His (see Figure 18-12), is the penetrating portion of the AV nodal system. It penetrates the fibrous cardiac skeleton and is the only electrically conductive connection between atrial and ventricular muscle masses. This penetrating portion of the bundle also has greater electrical resistance than regular cardiac muscle. A unique feature of the AV bundle is its one-way conduction from atria to ventricles. Ventricular impulses cannot be conducted backward through the bundle to the atria; this prevents reentry of the cardiac impulse back to the atria.

In summary, the AV nodal system consists of (1) junctional (transitional) fibers, (2) the node proper, and (3) the AV bundle (bundle of His). After they are depolarized, AV nodal fibers require a longer time to repolarize than any other cardiac fiber. The AV node is refractory to depolarizing stimuli longer than any other cardiac fiber.

Purkinje System Conduction

After it penetrates the fibrous cardiac skeleton, the AV bundle enters the intraventricular septum and divides into left and right bundle branches (see Figure 18-12). At the heart’s apex, smaller branches of each bundle spread throughout the ventricles back toward the base. These Purkinje fibers penetrate into the heart muscle a few millimeters and fuse with other ventricular muscle. Conduction velocity is greatly accelerated through these fibers (about 1.5 to 4 m per second). Ventricular muscle is almost instantly depolarized; about 0.03 second elapses from the time the impulse enters the bundle branches until it reaches the terminal Purkinje fibers. Conduction velocity through other ventricular muscle is only about one sixth the conduction velocity of the Purkinje fibers (0.3 to 0.5 m per second); only about 0.06 second is required for impulse transmission from bundle branches to the last ventricular muscle fiber. The total time required for impulse transmission from the SA node to the last ventricular fiber is normally about 0.22 second.¹

This uniform and rapid ventricular conduction is physiologically important for coordinated, synchronized contraction and relaxation. Synchronized ventricular action is necessary for normal cardiac output and ventricular filling.