BIPN100 F15 Human Physiology I (Kristan) Problem set #5 p. 1 1. Dantrolene has the same effect on smooth muscles as it has on skeletal muscle: it relaxes them by blocking the release of Ca ++ from the SR. Will dantrolene have a stronger, weaker, or the same effect on smooth muscle contraction as it has on skeletal muscle contraction?. Dantrolene will have e smaller effect on the contraction of smooth muscle, because much of the Ca ++ that regulates smooth muscle contraction enters the cytoplasm from the extracellular fluid, crossing the plasma membrane during Ca ++ -based action potentials. 2. Children have been known to chew on the leaves of rhubarb plants growing in their yard. Rhubarb contains large amounts of oxalic acid, a molecule that tightly binds Ca ++, and eating the leaves can be fatal. State at least two ways in which ingestion of oxalic acid may lead to death. If oxalic acid binds much of the Ca ++ in the blood and body fluids, the concentration of free Ca ++ outside cells will dramatically drop. Both smooth muscle and cardiac muscle depend upon extracellular Ca ++ to initiate and maintain contraction, so a drop in [Ca ++ ]plasma is exceedingly dangerous. The changes in smooth muscle contractions will be uncomfortable (e.g., intestinal distress, blood pressure changes, inability to focus your eyes), but the heart is the most vulnerable because the Ca ++ that causes contraction moves across the cell membrane from the extracellular fluids. A large drop in [Ca ++ ]plasma will stop the heartbeat. 3. The figure below shows the contractions of skeletal, cardiac, and smooth muscle. A. List 3 mechanisms that make the cardiac muscle contraction have a slower onset and a more prolonged time course than the skeletal muscle contraction. For each mechanism listed, say whether that mechanism causes a slower onset (SO), a more prolonged duration (PD), or both (B). Some possible answers:
BIPN100 F15 Human Physiology I (Kristan) Problem set #5 p. 2 1. Ca 2+ induced Ca 2+ release is slower than excitation-contraction coupling (SO) 2. longer action potential due to Ca 2+ entry and plateau phase (PD) 3. distance from SR is greater in cardiac muscle (B) 4. myosin in cardiac muscle has slower kinetics (B) 5. smaller SR (SO) 6. speed of myosin ATPases (B) 7. speed of Ca 2+ ATPase activity/ removal of Ca 2+ (PD) 8. slower Ca 2+ channels (SO) 9. slow K+ channels (SO) B. List 3 mechanisms that make the smooth muscle contraction have a slower onset and a more prolonged time course than the cardiac muscle contraction. For each mechanism, say whether that mechanism causes a slower onset (SO), a more prolonged duration (PD), or both (B). Some possible answers: 1. diffusion distance for Ca 2+ is larger in smooth muscle and there are no specialized receptor regions, so it takes longer to get actin/myosin, and for it to diffuse away (B) 2. cross bridges have slower kinetics (B) 3. ryanodine kinetics are slower in smooth muscle (SO) 4. longer actin/myosin filaments (PD) 5. less SR (B) 6. able to slide farther because no sarcomeres (PD) 7. latch state- dephosphorylated myosin attached to actin (PD) 8. less ATP needed, so it is much more efficient, can sustain contraction longer (PD) 9. catch property can hold onto contractions without energy use (PD) 10. MLCK (B) 11. depolarization is faster in cardiac muscle (B) 12. Ca 2+ reuptake is slow (PD) 4. A weakness in the ventricular wall can be a serious defect. In which ventricle would a weak spot be the most life-threatening? Why? The left ventricle develops a much higher pressure [normally 120 mm Hg at its peak, but it can be over 200 mm Hg in people with hypertension or during maximal exercise] than does the right ventricle [less than 20 mm Hg at its peak]. Thus, a weak spot in the left ventricular wall would be exposed to much higher pressure and would be more likely to break. [In fact, the most likely place for such a weakness to occur is in the aorta. Weak spots in the aorta - called "aortic aneurisms" - are exposed to the same high pressure as is the left ventricle.] 5. Compare the volume of blood pumped by the left side of the heart to the volume pumped by the right side of the heart. Predict which side would pump the most blood?
BIPN100 F15 Human Physiology I (Kristan) Problem set #5 p. 3 The right side of the heart and the left side of the heart must pump the same amount of blood. If they do not, two serious conditions result. First, if one ventricle of the heart cannot pump out the amount of blood that is returning to it, the chamber will become distended, stretching the heart muscle cells. If they are stretched into the region of their length-tension relationship in which they can generate only a little tension, the contraction of the heart is weakened further. Second, blood will back up in the vessels behind the side that is pumping less and edema results. Edema is less serious in the systemic tissues (when the right heart heart chambers fail) than in the lungs (when the left heart chambers fail). 6. Cardiac muscle fibers have a long refractory period, which is important for insuring that all parts of the heart contract simultaneously. How does the refractory period have this effect? Normally depolarization sweeps over the heart from top to bottom, so that contraction begins at the atria and moves through the ventricles to the apex of the heart, which moves blood efficiently into and out of the ventricles. Following depolarization, the heart cells become refractory. This period, during which the heart cells cannot depolarize again, prevents depolarization from reversing its direction and traveling back toward the atria. [ADDED NOTE: In certain pathological conditions, some myocardial fibers escape from their refractory period while other (damaged) neighboring myocardial fibers are still depolarized. Currents flowing in the depolarized regions can then reinvade the newly nonrefractory regions, a condition called "re-entry." As a result, part of a ventricle depolarizes and contracts independently of the rest of the heart. In extreme cases, small portions of the heart depolarize and repolarize at random (fibrillation). Asynchronous depolarization produces asynchronous contraction, and asynchronous contraction cannot move blood out of the heart and into the vessels.] 7. Why is the sino-atrial node commonly called the pacemaker of the heart? Why isn't the atrioventricular node the pacemaker? All the cells of the cardiac conduction system can depolarize autonomously, but the endogenous rhythmic depolarization of cells in the sino-atrial (SA) node occurs at the highest rate. Because they are electrically connected to all the rest of the cells in the heart, they drive the system at intrinsic rate of the SA node. The atrio-ventricular (AV) node gets reset with each wave caused by the SA node so under normal conditions, the AV node can never start a beat before the SA node. 8. If you were installing an artificial pacemaker into a patient, where would you want to place the electrodes?
BIPN100 F15 Human Physiology I (Kristan) Problem set #5 p. 4 The artificial pacemaker can cause action potentials at any location in the heart, because all cardiac muscles and conduction system are electrically connected to one another through large gap junctions. However, conduction would be most normal if the pacemaker were implanted near the heart's own conduction system, for example, near the AV node. In fact, because (1) ventricular contraction is most crucial to cardiac function, and (2) the AV node is the most likely point of conduction failure, placing the pacemaker at the AV node is the best location to avoid conduction block and to maintain efficient cardiac output. [An artificial pacemaker is a device that supplies rhythmic depolarization to the heart by generating periodic depolarizing electrical signals to the cardiac muscle. These devices are used when an individual's own heart no longer reliably depolarizes or efficiently conducts the depolarizing signal.] 9. P-wave T wave QRS complex A. Atrial contraction begins during the P wave; ventricular contraction and atrial relaxation ocurs during the QRS complex; and ventricular relaxation occurs during the T wave. B. The waves would look very much the same, unless there was a large amount of damage to the left ventricle. In that case, the QRS complex and the T wave might be somewhat smaller, but the timing of the waves would be normal. [In general, the ECG is related to electrical events and not mechanical events, and heart failure is primarily a mechanical failure.] 10A. Block in conduction through the A-V node [The A-V node is particularly prone to block like this. Conduction through the node has a low safety factor, because the conduction fibers in the node are small, but they must excite the large fibers in the ventricular septum enough to depolarize them above threshold for action potentials.] The record contains extra P waves that are not followed by a QRS complex. [If you had a longer recording, you might see that the P waves actually occur with one regular frequency and the QRS complexes occur with another regular, but slower frequency.] This record indicates that the atria of the heart are depolarizing (and you might infer,
BIPN100 F15 Human Physiology I (Kristan) Problem set #5 p. 5 contracting) with one rhythm, and the ventricles are depolarizing (and, presumably, contracting) with another, slower rhythm. B. Sinoatrial node block. The first depolarization looks normal: the P wave, QRS complex, and T wave are all recognizable. The second QRS complex and T wave are normal, but the P wave is smaller. The two depolarizations after the arrow lack a P wave altogether, which means that the atrium was not activated by the SA node. Notice, also, that the frequency of QRS complexes slowed noticeably after the P waves were no longer seen [i.e., there is a greater time between the second, the third, and the fourth records than there is between the first and second records], suggesting that the SA node has stopped functioning at around the arrow and one of the other conducting fibers (probably the AV node) has taken over as pacemaker. [The intrinsic frequency of spontaneous depolarization is fastest in the cells of the SA node, slower in the AV node, and slowest in the other pacemaker/conducting cells.[ C. Premature AV node beat. The first three P-QRS-T waves look normal, but the fourth has two abnormal properties: it lacks a P wave before the QRS complex and has two waves [probably a P and T] immediately after the QRS complex. After a delay, the fifth set of waves are normal. [When a premature beat is triggered by cells in an unusual location, the initiating site probably the AV node in this case--is called an ectopic focus.] D. Ventricular tachycardia. The last half of this record has several large, rapid and very large depolarizations; these depolarizations have no P waves between them. (The first half of the record contains several depolarizations that include the normal components, allowing you to observe the characteristic heart rate and the size of normal heart waves.) It is reasonable to conclude that this rapid heart rate is being driven by depolarization of the ventricles (because the waves are so large), and because there is no sign of P waves. [You would expect this part of the record to be accompanied by rapid contractions of the ventricular muscles. These rapid contractions are likely to be less efficient than normal contractions for at least two reasons: (1) filling time would be shortened and (2) without increased sympathetic activity to exert an inotropic effect on the mechanical properties of ventricular muscle, the ventricles will probably empty less efficiently than normal.] E. Ventricular fibrillation. This record shows many small, irregular depolarizations, with no large, repeated depolarizations like the QRS complex. These factors indicate that the ventricles are not depolarizing in an organized fashion. This is characteristic of ventricular fibrillation, which is a lack of organized contraction in the ventricular muscle.
BIPN100 F15 Human Physiology I (Kristan) Problem set #5 p. 6 [The record is sufficiently disorganized that it isn't possible to determine whether or not there are P waves. Notice that if a ventricle doesn t contract efficiently, within a very few minutes, a positive feedback situation occurs in which the myocardial cells-- overstretched and deprived of adequate coronary circulation--become less and less able to contract normally, so the heart may fill even more, stretching it even more, making it even weaker, and so on until the muscles cannot contract at all. The treatment of ventricular fibrillation must be prompt and effective.] 11. The size and polarity of voltage changes recorded by any one EKG lead reflects only particular vectorial components of potential changes moving through the heart, mostly from the part of the heart closest to the two electrodes being recorded. Because the various leads are placed in different positions around the body, different leads record different components of the net current vector, even though they are recording exactly the same event.