Guyton and Hall Physiology - Chapter 10: Rhythmical Excitation of the Heart PDF

CHAPTER 10 UNIT III Rhythmical Excitation of the Heart The human heart has a special system for rhythmic and...

CHAPTER 10 UNIT III Rhythmical Excitation of the Heart The human heart has a special system for rhythmic and 1 mm thick. It is located in the superior posterolateral self-excitation and repetitive contraction approximately wall of the right atrium immediately below and slightly 100,000 times each day or 3 billion times in the average lateral to the opening of the superior vena cava. The fibers human lifetime. This impressive feat is performed by a of this node have almost no contractile muscle filaments system that does the following: (1) generates electrical and are each only 3 to 5 micrometers (μm) in diameter, in impulses to initiate rhythmical contraction of the heart contrast to a diameter of 10 to 15 μm for the surround- muscle; and (2) conducts these impulses rapidly through ing atrial muscle fibers. However, the sinus nodal fibers the heart. When this system functions normally, the atria connect directly with the atrial muscle fibers, so that any contract about one-sixth of a second ahead of ventricular action potential that begins in the sinus node spreads contraction, which allows filling of the ventricles before immediately into the atrial muscle wall. they pump blood through the lungs and peripheral circu- lation. Another especially important feature of the system AUTOMATIC ELECTRICAL RHYTHMICITY is that it allows all portions of the ventricles to contract OF THE SINUS FIBERS almost simultaneously, which is essential for the most effective pressure generation in the ventricular chambers. Some cardiac fibers have the capability of self-excitation, This rhythmical and conductive system of the heart a process that can cause automatic rhythmical discharge is susceptible to damage by heart disease, especially by and contraction. This capability is especially true of the ischemia resulting from inadequate coronary blood flow. heart’s specialized conducting system, including fibers of The effect is often a bizarre heart rhythm or an abnor- the sinus node. For this reason, the sinus node ordinarily mal sequence of contraction of the heart chambers, and controls the beat rate of the entire heart, as discussed in the pumping effectiveness of the heart can be affected detail later in this chapter. First, let us describe this auto- severely, even to the extent of causing death. matic rhythmicity. Mechanism of Sinus Nodal Rhythmicity. Figure 10- SPECIALIZED EXCITATORY AND 2 shows action potentials recorded from inside a sinus CONDUCTIVE SYSTEM OF THE HEART nodal fiber for three heartbeats and, by comparison, a Figure 10-1 shows the specialized excitatory and con- single ventricular muscle fiber action potential. Note ductive system of the heart that controls cardiac con- that the resting membrane potential of the sinus nodal tractions. The figure shows the sinus node (also called fiber between discharges is about –55 to –60 millivolts, sinoatrial [S-A] node), in which the normal rhythmical in comparison with –85 to –90 millivolts for the ventricu- impulses are generated; the internodal pathways that con- lar muscle fiber. The cause of this lower negativity is that duct impulses from the sinus node to the atrioventricular the cell membranes of the sinus fibers are naturally leaky (A-V) node; the A-V node in which impulses from the to sodium and calcium ions, and positive charges of the atria are delayed before passing into the ventricles; the entering sodium and calcium ions neutralize some of the A-V bundle, which conducts impulses from the atria into intracellular negativity. the ventricles; and the left and right bundle branches of Before we explain the rhythmicity of the sinus nodal Purkinje fibers, which conduct the cardiac impulses to all fibers, first recall from the discussions of Chapters 5 and 9 parts of the ventricles. that cardiac muscle has three main types of membrane ion channels that play important roles in causing the voltage changes of the action potential. They are (1) fast sodium SINUS (SINOATRIAL) NODE channels, (2) calcium channels (particularly L-type or The sinus node is a small, flattened, ellipsoid strip of spe- “slow” calcium channels), and (3) potassium channels (see cialized cardiac muscle about 3 mm wide, 15 mm long, Figure 9-5). 127 UNIT III The Heart for more than a few milliseconds, the inactivation gates on the inside of the cell membrane that close the fast sodium channels become closed and remain so. There- fore, only the slow sodium-calcium channels can open (i.e., can become activated) and thereby cause the action potential. As a result, the atrial nodal action potential is A-V bundle slower to develop than the action potential of the ventric- Sinus node ular muscle. Also, after the action potential does occur, return of the potential to its negative state occurs slowly Internodal Left as well, rather than the abrupt return that occurs for the pathways bundle ventricular fiber. branch A-V node Leakiness of Sinus Nodal Fibers to Sodium and Cal- Right cium Causes Self-Excitation. Because of the high sodi- bundle branch um ion concentration in the extracellular fluid outside the nodal fiber, as well as a moderate number of already open sodium channels, positive sodium ions from outside the fibers normally tend to leak to the inside through inward, “funny” currents. Therefore, between heartbeats, the in- Figure 10-1 Sinus node and the Purkinje system of the heart, show- ing also the atrioventricular (A-V) node, atrial internodal pathways, flux of positively charged sodium ions causes a slow rise and ventricular bundle branches. in the resting membrane potential in the positive direc- tion. Thus, as shown in Figure 10-2, the resting potential +20 Threshold for Sinus Ventricular gradually rises and becomes less negative between each discharge nodal fiber muscle fiber two heartbeats. When the potential reaches a threshold 0 voltage of about –40 millivolts, the L-type calcium chan- nels become activated, thus causing the action potential. Millivolts Therefore, basically, the inherent leakiness of the sinus –40 nodal fibers to sodium and calcium ions causes their self- excitation. Resting Why does this leakiness to sodium and calcium ions –80 potential not cause the sinus nodal fibers to remain depolarized all the time? Two events occur during the course of the 0 1 2 3 action potential to prevent such a constant state of depo- Seconds larization. First, the L-type calcium channels become Figure 10-2 Rhythmical discharge of a sinus nodal fiber. Also, the inactivated (i.e., they close) within about 100 to 150 mil- sinus nodal action potential is compared with that of a ventricular liseconds after opening; and second, at about the same muscle fiber. time, greatly increased numbers of potassium channels open. Therefore, influx of positive calcium and sodium Opening of the fast sodium channels for a few ions through the L-type calcium channels ceases, while 10,000ths of a second is responsible for the rapid upstroke at the same time large quantities of positive potassium spike of the action potential observed in ventricular mus- ions diffuse out of the fiber. Both these effects reduce the cle because of rapid influx of positive sodium ions to the intracellular potential back to its negative resting level and interior of the fiber. Then, the plateau of the ventricular therefore terminate the action potential. Furthermore, the action potential is caused primarily by slower opening of potassium channels remain open for another few tenths the slow sodium-calcium channels, which lasts for about of a second, temporarily continuing movement of posi- 0.3 second. Finally, opening of potassium channels allows tive charges out of the cell, with resultant excess negativity for the diffusion of large amounts of positive potassium inside the fiber; this process is called hyperpolarization. ions in the outward direction through the fiber membrane The hyperpolarization state initially carries the resting and returns the membrane potential to its resting level. membrane potential down to about –55 to –60 millivolts However, there is a difference in the function of these at the termination of the action potential. channels in the sinus nodal fiber because the resting Why is this new state of hyperpolarization not main- potential is much less negative—only –55 millivolts in tained forever? The reason is that during the next few the nodal fiber instead of the –90 millivolts in the ven- tenths of a second after the action potential is over, pro- tricular muscle fiber. At this level of –55 millivolts, the gressively more and more potassium channels close. The fast sodium channels mainly have already become inacti- inward-leaking sodium (“funny” current) and calcium vated, or blocked. This is because any time the membrane ions once again overbalance the outward flux of potas- potential remains less negative than about –55 millivolts sium ions, which causes the resting potential to drift 128  Chapter 10 Rhythmical Excitation of the Heart Internodal rapidly conducting Purkinje fibers of the ventricles, dis- pathways Transitional fibers cussed below. THE ATRIOVENTRICULAR NODE DELAYS A-V node IMPULSE CONDUCTION FROM THE ATRIA UNIT III TO THE VENTRICLES (0.03) The atrial conductive system is organized so that the car- Atrioventricular diac impulse does not travel from the atria into the ven- fibrous tissue tricles too rapidly; this delay allows time for the atria to (0.12) Penetrating portion empty their blood into the ventricles before ventricular of A-V bundle contraction begins. It is primarily the A-V node and its Distal portion of adjacent conductive fibers that delay this transmission A-V bundle into the ventricles. The A-V node is located in the posterior wall of the Right bundle branch Left bundle branch right atrium, immediately behind the tricuspid valve, as (0.16) shown in Figure 10-1. Figure 10-3 diagrams the differ- ent parts of this node, plus its connections with the enter- ing atrial internodal pathway fibers and the exiting A-V bundle. This figure also shows the approximate intervals Ventricular of time (in fractions of a second) between the initial onset septum of the cardiac impulse in the sinus node and its subse- Figure 10-3 Organization of the atrioventricular (A-V) node. The quent appearance in the A-V nodal system. Note that the numbers represent the interval of time from the origin of the impulse impulse, after traveling through the internodal pathways, in the sinus node. The values have been extrapolated to humans. reaches the A-V node about 0.03 second after its origin in the sinus node. Then, there is a delay of another 0.09 sec- upward once more, finally reaching the threshold level ond in the A-V node itself before the impulse enters the for discharge at a potential of about –40 millivolts. Then, penetrating portion of the A-V bundle, where it passes the entire process begins again: self-excitation to cause into the ventricles. A final delay of another 0.04 second the action potential, recovery from the action potential, occurs mainly in this penetrating A-V bundle, which is hyperpolarization after the action potential is over, drift of composed of multiple small fascicles passing through the the resting potential to threshold, and finally re-excitation fibrous tissue separating the atria from the ventricles. to elicit another cycle. This process continues throughout Thus, the total delay in the A-V nodal and A-V bundle a person’s life. system is about 0.13 second. This delay, in addition to the initial conduction delay of 0.03 second from the sinus node to the A-V node, makes a total delay of 0.16 second INTERNODAL AND INTERATRIAL PATHWAYS before the excitatory signal finally reaches the contracting TRANSMIT CARDIAC IMPULSES THROUGH muscle of the ventricles. THE ATRIA The ends of the sinus nodal fibers connect directly with Cause of the Slow Conduction. The slow conduction in the surrounding atrial muscle fibers. Therefore, action the transitional, nodal, and penetrating A-V bundle fibers potentials originating in the sinus node travel outward is caused mainly by diminished numbers of gap junctions into these atrial muscle fibers. In this way, the action between successive cells in the conducting pathways, so potential spreads through the entire atrial muscle mass there is great resistance to conduction of excitatory ions and, eventually, to the A-V node. The velocity of conduc- from one conducting fiber to the next. Therefore, it is easy tion in most atrial muscle is about 0.3 m/sec, but conduc- to see why each succeeding cell is slow to be excited. tion is more rapid, about 1 m/sec, in several small bands RAPID TRANSMISSION OF THE CARDIAC of atrial fibers. One of these bands, called the anterior IMPULSE IN THE VENTRICULAR PURKINJE interatrial band (also called Bachman’s bundle), passes SYSTEM through the anterior walls of the atria to the left atrium. In addition, three other small bands curve through the ante- Special Purkinje fibers lead from the A-V node through rior, lateral, and posterior atrial walls and terminate in the the A-V bundle into the ventricles. Except for the initial A-V node, shown in Figure 10-1 and Figure 10-3; these portion of these fibers, where they penetrate the A-V are called, respectively, the anterior, middle, and posterior fibrous barrier, they have functional characteristics that internodal pathways. The cause of more rapid velocity of are the opposite of those of the A-V nodal fibers. They are conduction in these bands is the presence of specialized very large fibers, even larger than the normal ventricu- conduction fibers. These fibers are similar to even more lar muscle fibers, and they transmit action potentials at a 129 UNIT III The Heart velocity of 1.5 to 4.0 m/sec, a velocity about six times that TRANSMISSION OF THE CARDIAC in the usual ventricular muscle and 150 times that in some IMPULSE IN THE VENTRICULAR MUSCLE of the A-V nodal fibers. This velocity allows almost instan- taneous transmission of the cardiac impulse throughout Once the impulse reaches the ends of the Purkinje fibers, the entire remainder of the ventricular muscle. it is transmitted through the ventricular muscle mass by The rapid transmission of action potentials by Pur- the ventricular muscle fibers themselves. The velocity of kinje fibers is believed to be caused by a very high level of transmission is now only 0.3 to 0.5 m/sec, one-sixth that permeability of the gap junctions at the intercalated discs in the Purkinje fibers. between the successive cells that make up the Purkinje The cardiac muscle wraps around the heart in a double fibers. Therefore, ions are transmitted easily from one cell spiral, with fibrous septa between the spiraling layers; there- to the next, thus enhancing the velocity of transmission. fore, the cardiac impulse does not necessarily travel directly The Purkinje fibers also have very few myofibrils, which outward toward the surface of the heart but, instead, angu- means that they contract little or not at all during the lates toward the surface along the directions of the spirals. course of impulse transmission. Because of this angulation, transmission from the endocardial surface to the epicardial surface of the ventricle requires as The A-V Bundle Is Normally a One-Way Conduction much as another 0.03 second, approximately equal to the time Path. A special characteristic of the A-V bundle is the required for transmission through the entire ventricular por- inability, except in abnormal states, of action potentials tion of the Purkinje system. Thus, the total time for transmis- to travel backward from the ventricles to the atria. This sion of the cardiac impulse from the initial bundle branches to characteristic prevents re-entry of cardiac impulses by the last of the ventricular muscle fibers in the normal heart is this route from the ventricles to the atria, allowing only about 0.06 second. forward conduction from the atria to the ventricles. Furthermore, it should be recalled that everywhere, SUMMARY OF THE SPREAD OF THE except at the A-V bundle, the atrial muscle is separated CARDIAC IMPULSE THROUGH THE HEART from the ventricular muscle by a continuous fibrous bar- Figure 10-4 summarizes the transmission of the cardiac rier, a portion of which is shown in Figure 10-3. This impulse through the human heart. The numbers on the barrier normally acts as an insulator to prevent passage of the cardiac impulse between atrial and ventricular muscle through any other route besides forward conduc- tion through the A-V bundle. In rare cases, an abnormal muscle bridge, or accessory pathway, does penetrate the fibrous barrier elsewhere besides at the A-V bundle. Under such conditions, the cardiac impulse can re-enter the atria from the ventricles and cause serious cardiac arrhythmias. Distribution of the Purkinje Fibers in the Ventricles— Left and Right Bundle Branches. After penetrating the fibrous tissue between the atrial and ventricular muscle, the distal portion of the A-V bundle passes downward in the ven-.07 S-A tricular septum for 5 to 15 mm toward the apex of the heart,.04.06 as shown in Figures 10-1 and 10-3. Then, the bundle divides.03.09 into left and right bundle branches that lie beneath the endo- A-V.00.22 cardium on the two respective sides of the ventricular sep-.07 tum. Each branch spreads downward toward the apex of the.03.19.16 ventricle, progressively dividing into smaller branches. These.05 branches, in turn, course sidewise around each ventricular.18.21 chamber and back toward the base of the heart. The ends of.07.17 the Purkinje fibers penetrate about one-third of the way into.19.17 the muscle mass and finally become continuous with the car- diac muscle fibers..18 The total elapsed time averages only 0.03 second from the time the cardiac impulse enters the bundle branches.21 in the ventricular septum until it reaches the termina-.20 tions of the Purkinje fibers. Therefore, once the cardiac Figure 10-4 Transmission of the cardiac impulse through the heart, impulse enters the ventricular Purkinje conductive sys- showing the time of appearance (in fractions of a second after initial tem, it spreads almost immediately to the entire ventricu- appearance at the sinoatrial node) in different parts of the heart. A-V, lar muscle mass. Atrioventricular; S-A, sinoatrial. 130  Chapter 10 Rhythmical Excitation of the Heart figure represent the intervals of time, in fractions of a sec- discharge rate that is more rapid than that of the sinus ond, that lapse between the origin of the cardiac impulse node. For example, this development sometimes occurs in in the sinus node and its appearance at each respective the A-V node or in the Purkinje fibers when one of these point in the heart. Note that the impulse spreads at mod- becomes abnormal. In either case, the pacemaker of the erate velocity through the atria but is delayed more than heart shifts from the sinus node to the A-V node or to the UNIT III 0.1 second in the A-V nodal region before appearing in excited Purkinje fibers. Under rarer conditions, a place in the ventricular septal A-V bundle. Once it has entered the atrial or ventricular muscle develops excessive excit- this bundle, it spreads very rapidly through the Purkinje ability and becomes the pacemaker. fibers to the entire endocardial surfaces of the ventricles. A pacemaker elsewhere than the sinus node is called Then, the impulse once again spreads slightly less rapidly an ectopic pacemaker. An ectopic pacemaker causes an through the ventricular muscle to the epicardial surfaces. abnormal sequence of contraction of the different parts It is important that the student learn in detail the of the heart and can cause significant weakening of heart course of the cardiac impulse through the heart and the pumping. precise times of its appearance in each separate part of the Another cause of shift of the pacemaker is blockage of heart. A thorough quantitative knowledge of this process transmission of the cardiac impulse from the sinus node is essential for understanding electrocardiography, which to the other parts of the heart. The new pacemaker then is discussed in Chapters 11 through 13. usually occurs at the A-V node or in the penetrating por- tion of the A-V bundle on the way to the ventricles. When A-V block occurs—that is, when the cardiac CONTROL OF EXCITATION AND impulse fails to pass from the atria into the ventricles CONDUCTION IN THE HEART through the A-V nodal and bundle system—the atria con- tinue to beat at the normal rate of rhythm of the sinus THE SINUS NODE IS THE NORMAL PACE- node while a new pacemaker usually develops in the Pur- MAKER OF THE HEART kinje system of the ventricles and drives the ventricular In discussing the genesis and transmission of the cardiac muscle at a new rate, somewhere between 15 and 40 beats impulse through the heart, we have noted that the impulse per minute. After sudden A-V bundle block, the Purkinje normally arises in the sinus node. In some abnormal con- system does not begin to emit its intrinsic rhythmical ditions, this is not the case. Other parts of the heart can impulses until 5 to 20 seconds later because, before the also exhibit intrinsic rhythmical excitation in the same blockage, the Purkinje fibers had been “overdriven” by way as the sinus nodal fibers; this is particularly true of the rapid sinus impulses and, consequently, are in a sup- the A-V nodal and Purkinje fibers. pressed state. During these 5 to 20 seconds, the ventricles The A-V nodal fibers, when not stimulated from some fail to pump blood, and the person faints after the first 4 outside source, discharge at an intrinsic rhythmical rate to 5 seconds because of lack of blood flow to the brain. of 40 to 60 times per minute, and the Purkinje fibers dis- This delayed pickup of the heartbeat is called Stokes- charge at a rate somewhere between 15 and 40 times per Adams syndrome. If the delay period is too long, it can minute. These rates are in contrast to the normal rate of lead to death. the sinus node of 70 to 80 times per minute. Why then does the sinus node rather than the A-V ROLE OF THE PURKINJE SYSTEM IN node or the Purkinje fibers control the heart’s rhythmic- CAUSING SYNCHRONOUS CONTRACTION ity? The answer derives from the fact that the discharge OF THE VENTRICULAR MUSCLE rate of the sinus node is considerably faster than the natu- ral self-excitatory discharge rate of either the A-V node or The rapid conduction of the Purkinje system normally the Purkinje fibers. Each time the sinus node discharges, its permits the cardiac impulse to arrive at almost all por- impulse is conducted into both the A-V node and Purkinje tions of the ventricles within a narrow span of time, excit- fibers, also discharging their excitable membranes. How- ing the first ventricular muscle fiber only 0.03 to 0.06 ever, the sinus node discharges again before either the A-V second ahead of excitation of the last ventricular muscle node or Purkinje fibers can reach their own thresholds for fiber. This timing causes all portions of the ventricular self-excitation. Therefore, the new impulse from the sinus muscle in both ventricles to begin contracting at almost node discharges both the A-V node and Purkinje fibers the same time and then to continue contracting for about before self-excitation can occur in either of these sites. another 0.3 second. Thus, the sinus node controls the beat of the heart Effective pumping by the two ventricular chambers because its rate of rhythmical discharge is faster than that requires this synchronous type of contraction. If the car- of any other part of the heart. Therefore, the sinus node is diac impulse should travel through the ventricles slowly, almost always the pacemaker of the normal heart. much of the ventricular mass would contract before contraction of the remainder, in which case the overall Abnormal Pacemakers—Ectopic Pacemaker. Occasio- pumping effect would be greatly depressed. Indeed, in nally, some other part of the heart develops a rhythmical some types of cardiac dysfunction, several of which are 131 UNIT III The Heart discussed in Chapters 12 and 13, slow transmission does −75 millivolts rather than the normal level of −55 to −60 occur, and the pumping effectiveness of the ventricles is millivolts. Therefore, the initial rise of the sinus nodal decreased as much as 20% to 30%. Implantable cardiac membrane potential caused by inward sodium and cal- resynchronization devices are types of pacemakers using cium leakage requires much longer to reach the threshold electrical wires or leads that can be inserted into the car- potential for excitation. This requirement greatly slows diac chambers to restore appropriate timing between the the rate of rhythmicity of these nodal fibers. If the vagal atria and both ventricles to improve pumping effective- stimulation is strong enough, it is possible to stop the ness in patients with enlarged and weakened hearts. rhythmical self-excitation of this node entirely. In the A-V node, a state of hyperpolarization caused by vagal stimulation makes it difficult for the small atrial SYMPATHETIC AND PARASYMPATHETIC fibers entering the node to generate enough electricity NERVES CONTROL HEART RHYTHMICITY to excite the nodal fibers. Therefore, the safety factor for AND IMPULSE CONDUCTION BY THE transmission of the cardiac impulse through the transi- CARDIAC NERVES tional fibers into the A-V nodal fibers decreases. A mod- The heart is supplied with both sympathetic and para- erate decrease simply delays conduction of the impulse, sympathetic nerves, as shown in Figure 9-14 of Chapter but a large decrease blocks conduction entirely. 9. The parasympathetic nerves (the vagi) are distributed mainly to the S-A and A-V nodes, to a lesser extent to Sympathetic Stimulation Increases the Cardiac the muscle of the two atria, and very little directly to the Rhythm and Conduction. Sympathetic stimulation ventricular muscle. The sympathetic nerves, conversely, causes essentially the opposite effects on the heart as are distributed to all parts of the heart, with strong rep- those caused by vagal stimulation, as follows. resentation in the ventricular muscle, as well as in all the 1. It increases the rate of sinus nodal discharge. other areas. 2. It increases the rate of conduction, as well as the level of excitability in all portions of the heart. Parasympathetic (Vagal) Stimulation Slows the Cardi- 3. It increases greatly the force of contraction of all the ac Rhythm and Conduction. Stimulation of the parasym- cardiac musculature, both atrial and ventricular, as pathetic nerves to the heart (the vagi) causes acetylcholine discussed in Chapter 9. to be released at the vagal endings. This neurotransmitter In short, sympathetic stimulation increases the overall has two major effects on the heart. First, it decreases the activity of the heart. Maximal stimulation can almost tri- rate of rhythm of the sinus node, and second, it decreases ple the heartbeat frequency and can increase the strength the excitability of the A-V junctional fibers between the of heart contraction as much as twofold. atrial musculature and the A-V node, thereby slowing transmission of the cardiac impulse into the ventricles. Mechanism of the Sympathetic Effect. Stimulation of Weak to moderate vagal stimulation slows the rate of the sympathetic nerves releases norepinephrine at the heart pumping, often to as little as one-half normal. Fur- sympathetic nerve endings. Norepinephrine, in turn, thermore, strong stimulation of the vagi can completely stimulates beta-1 adrenergic receptors, which mediate the stop the rhythmical excitation by the sinus node or com- effects on heart rate. The precise mechanism whereby be- pletely block transmission of the cardiac impulse from the ta-1 adrenergic stimulation acts on cardiac muscle fibers atria into the ventricles through the A-V node. In either is somewhat unclear, but is thought to increase the per- case, rhythmical excitatory signals are no longer transmit- meability of the fiber membrane to sodium and calcium ted into the ventricles. The ventricles may stop beating for ions. In the sinus node, an increase of sodium-calcium 5 to 20 seconds, but then some small area in the Purkinje permeability causes a more positive resting potential. It fibers, usually in the ventricular septal portion of the A-V also causes an increased rate of upward drift of the di- bundle, develops a rhythm of its own and causes ventricu- astolic membrane potential toward the threshold level lar contraction at a rate of 15 to 40 beats per minute. This for self-excitation, thus accelerating self-excitation and, phenomenon is called ventricular escape. therefore, increasing the heart rate. In the A-V node and A-V bundles, increased sodium- Mechanism of the Vagal Effects. The acetylcholine re- calcium permeability makes it easier for the action poten- leased at the vagal nerve endings greatly increases the per- tial to excite each succeeding portion of the conducting meability of the fiber membranes to potassium ions, which fiber bundles, thereby decreasing the conduction time allows rapid leakage of potassium out of the conductive fib- from the atria to the ventricles. ers. This process causes increased negativity inside the fibers, The increase in permeability to calcium ions is at an effect called hyperpolarization, which makes this excitable least partially responsible for the increase in contractile tissue much less excitable, as explained in Chapter 5. strength of the cardiac muscle under the influence of In the sinus node, the state of hyperpolarization makes sympathetic stimulation. This is because calcium ions the resting membrane potential of the sinus nodal fibers play a powerful role in exciting the contractile process of considerably more negative than usual—that is, −65 to the myofibrils. 132  Chapter 10 Rhythmical Excitation of the Heart Bibliography Leyva F, Nisam S, Auricchio: 20 years of cardiac resynchronization therapy. J Am Coll Cardiol. 64:1047, 2014. 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