BRS Practice BMS PDF

Action Potential 1. The correct temporal sequence for events at the neuromuscular junction is a) action potential in the motor nerve; depolarization of the muscle end plate; uptake of Ca2+ into the presynaptic nerve terminal (b) uptake of Ca2+ into the presynaptic terminal; release of acetylcholine...

Action Potential 1. The correct temporal sequence for events at the neuromuscular junction is a) action potential in the motor nerve; depolarization of the muscle end plate; uptake of Ca2+ into the presynaptic nerve terminal (b) uptake of Ca2+ into the presynaptic terminal; release of acetylcholine (ACh); depolarization of the muscle end plate (C) release of ACh; action potential in the motor nerve; action potential in the muscle (D) uptake of Ca2+ into the motor end plate; action potential in the motor end plate; action potential in the muscle (e) release of ACh; action potential in the muscle end plate; action potential in the muscle The answer is b. Acetylcholine (ACh) is stored in vesicles and is released when an action potential in the motor nerve opens Ca2+ channels in the presynaptic terminal. ACh diffuses across the synaptic cleft and opens Na+ and K+ channels in the muscle end plate, depolarizing it (but not producing an action potential). Depolarization of the muscle end plate causes local currents in adjacent muscle membrane, depolarizing the membrane to threshold and producing action potentials. 2. Which characteristic or component is shared by skeletal muscle and smooth muscle? (a) Thick and thin filaments arranged in sarcomeres (b) Troponin (c) Elevation of intracellular [Ca2+] for excitation–contraction coupling (D) Spontaneous depolarization of the membrane potential (e) High degree of electrical coupling between cells The answer is C. An elevation of intracellular [Ca2+] is common to the mechanism of excitation–contraction coupling in skeletal and smooth muscle. In skeletal muscle, Ca2+ binds to troponin C, initiating the cross-bridge cycle. In smooth muscle, Ca2+ binds to calmodulin. The Ca2+–calmodulin complex activates myosin light chain kinase, which phosphorylates myosin so that shortening can occur. The striated appearance of the sarcomeres and the presence of troponin are characteristic of skeletal, not smooth, muscle. Spontaneous depolarizations and gap junctions are characteristics of unitary smooth muscle but not skeletal muscle. 3. Repeated stimulation of a skeletal muscle fiber causes a sustained contraction (tetanus). Accumulation of which solute in intracellular fluid is responsible for the tetanus? (a) Na+ (b) K+ (c) Cl− (d) Mg2+ (e) Ca2+ (f) Troponin (g) Calmodulin (h) Adenosine triphosphate (ATP) The answer is e. During repeated stimulation of a muscle fiber, Ca2+ is released from the sarcoplasmic reticulum (SR) more quickly than it can be reaccumulated; therefore, the intracellular [Ca2+] does not return to resting levels as it would after a single twitch. The increased [Ca2+] allows more cross-bridges to form and, therefore, produces increased tension (tetanus). Intracellular Na+ and K+ concentrations do not change during the action potential. Very few Na+ or K+ ions move into or out of the muscle cell, so bulk concentrations are unaffected. Adenosine triphosphate (ATP) levels would, if anything, decrease during tetanus. 4. A 42-year-old man with myasthenia gravis notes increased muscle strength when he is treated with an acetylcholinesterase (AChE) inhibitor. The basis for his improvement is increased (a) amount of acetylcholine (ACh) released from motor nerves (b) levels of ACh at the muscle end plates (c) number of ACh receptors on the muscle end plates (d) amount of norepinephrine released from motor nerves (e) synthesis of norepinephrine in motor nerves The answer is b. Myasthenia gravis is characterized by a decreased density of acetylcholine (ACh) receptors at the muscle end plate. An acetylcholinesterase (AChE) inhibitor blocks degradation of ACh in the neuromuscular junction, so levels at the muscle end plate remain high, partially compensating for the deficiency of receptors. 5. During a nerve action potential, a stimulus is delivered as indicated by the arrow shown in the following figure. In response to the stimulus, a second action potential (a) of smaller magnitude will occur (b) of normal magnitude will occur (c) of normal magnitude will occur but will be delayed (d) will occur but will not have an overshoot (e) will not occur The answer is e. Because the stimulus was delivered during the absolute refractory period, no action potential occurs. The inactivation gates of the Na+ channel was closed by depolarization and remain closed until the membrane is repolarized. As long as the inactivation gates are closed, the Na+ channels cannot be opened to allow for another action potential. 6. A muscle cell has an intracellular [Na+] of 14 mM and an extracellular [Na+] of 140 mM. Assuming that 2.3 RT/F = 60 mV, what would the membrane potential be if the muscle cell membrane were permeable only to Na+? (a) 80 mV (b) −60 mV (c) 0 mV (d) +60 mV (e) +80 mV The answer is D. The Nernst equation is used to calculate the equilibrium potential for a single ion. In applying the Nernst equation, we assume that the membrane is freely permeable to that ion alone. ENa+ = 2.3 RT/zF log Ce/Ci = 60 mV log 140/14 = 60 mV log 10 = 60 mV. Notice that the signs were ignored, and that the higher concentration was simply placed in the numerator to simplify the log calculation. To determine whether ENa+ is +60 mV or −60 mV, use the intuitive approach—Na+ will diffuse from extracellular to intracellular fluid down its concentration gradient, making the cell interior positive. Questions 7–9 The following diagram of a nerve action potential applies to Questions 7–9. 7. At which labeled point on the action potential is K+ closest to electrochemical equilibrium? (a) 1 (b) 2 (c) 3 (d) 4 (e) 5 The answer is e. The hyperpolarizing afterpotential represents the period during which K+ permeability is highest, and the membrane potential is closest to the K+ equilibrium potential. At that point, K+ is closest to electrochemical equilibrium. The force driving K+ movement out of the cell down its chemical gradient is balanced by the force driving K+ into the cell down its electrical gradient. 8. What process is responsible for the change in membrane potential that occurs between point 1 and point 3? (a) Movement of Na+ into the cell (b) Movement of Na+ out of the cell (c) Movement of K+ into the cell (d) Movement of K+ out of the cell (e) Activation of the Na+–K+ pump (f) Inhibition of the Na+–K+ pump The answer is a. The upstroke of the nerve action potential is caused by opening of the Na+ channels (once the membrane is depolarized to threshold). When the Na+ channels open, Na+ moves into the cell down its electrochemical gradient, driving the membrane potential toward the Na+ equilibrium potential. 9. What process is responsible for the change in membrane potential that occurs between point 3 and point 4? (a) Movement of Na+ into the cell (b) Movement of Na+ out of the cell (c) Movement of K+ into the cell (d) Movement of K+ out of the cell (e) Activation of the Na+–K+ pump (f) Inhibition of the Na+–K+ pump The answer is D. The process responsible for repolarization is the opening of K+ channels. The K+ permeability becomes very high and drives the membrane potential toward the K+ equilibrium potential by flow of K+ out of the cell. 10. The velocity of conduction of action potentials along a nerve will be increased by (a) stimulating the Na+–K+ pump (b) inhibiting the Na+–K+ pump (c) decreasing the diameter of the nerve (d) myelinating the nerve (e) lengthening the nerve fiber The answer is D. Myelin insulates the nerve, thereby increasing conduction velocity; action potentials can be generated only at the nodes of Ranvier, where there are breaks in the insulation. Activity of the Na+–K+ pump does not directly affect the formation or conduction of action potentials. Decreasing nerve diameter would increase internal resistance and, therefore, slow the conduction velocity. 11. A newly developed local anesthetic blocks Na+ channels in nerves. Which of the following effects on the action potential would it be expected to produce? (a) Decrease the rate of rise of the upstroke of the action potential (b) Shorten the absolute refractory period (c) Abolish the hyperpolarizing afterpotential (d) Increase the Na+ equilibrium potential (e) Decrease the Na+ equilibrium potential The answer is a. Blockade of the Na+ channels would prevent action potentials. The upstroke of the action potential depends on the entry of Na+ into the cell through these channels and therefore would also be reduced or abolished. The absolute refractory period would be lengthened because it is based on the availability of the Na+ channels. The hyperpolarizing afterpotential is related to increased K+ permeability. The Na+ equilibrium potential is calculated from the Nernst equation and is the theoretical potential at electrochemical equilibrium (and does not depend on whether the Na+ channels are open or closed). 12. At the muscle end plate, acetylcholine (ACh) causes the opening of (a) Na+ channels and depolarization toward the Na+ equilibrium potential (b) K+ channels and depolarization toward the K+ equilibrium potential (c) Ca2+ channels and depolarization toward the Ca2+ equilibrium potential (d) Na+ and K+ channels and depolarization to a value halfway between the Na+ and K+ equilibrium potentials (e) Na+ and K+ channels and hyperpolarization to a value halfway between the Na+ and K+ equilibrium potentials The answer is D. Binding of acetylcholine (ACh) to receptors in the muscle end plate opens channels that allow passage of both Na+ and K+ ions. Na+ ions will flow into the cell down its electrochemical gradient, and K+ ions will flow out of the cell down its electrochemical gradient. The resulting membrane potential will be depolarized to a value that is approximately halfway between their respective equilibrium potentials. 13. An inhibitory postsynaptic potential (a) depolarizes the postsynaptic membrane by opening Na+ channels (b) depolarizes the postsynaptic membrane by opening K+ channels (c) hyperpolarizes the postsynaptic membrane by opening Ca2+ channels (d) hyperpolarizes the postsynaptic membrane by opening Cl− channels The answer is D. An inhibitory postsynaptic potential hyperpolarizes the postsynaptic membrane, taking it farther from threshold. Opening Cl− channels would hyperpolarize the postsynaptic membrane by driving the membrane potential toward the Cl− equilibrium potential (about −90 mV). Opening Ca2+ channels would depolarize the postsynaptic membrane by driving it toward the Ca2+ equilibrium potential. 14. Which of the following would occur as a result of the inhibition of Na+, K+-ATPase? (a) Decreased intracellular Na+ concentration (b) Increased intracellular K+ concentration (c) Increased intracellular Ca2+ concentration (d) Increased Na+–glucose cotransport (e) Increased Na+–Ca2+ exchange The answer is C. Inhibition of Na+, K+-adenosine triphosphatase (ATPase) leads to an increase in intracellular Na+ concentration. Increased intracellular Na+ concentration decreases the Na+ gradient across the cell membrane, thereby inhibiting Na+–Ca2+ exchange and causing an increase in intracellular Ca2+ concentration. Increased intracellular Na+ concentration also inhibits Na+–glucose cotransport. 15. Which of the following temporal sequences is correct for excitation– contraction coupling in skeletal muscle? (a) Increased intracellular [Ca2+]; action potential in the muscle membrane; cross-bridge formation (b) Action potential in the muscle membrane; depolarization of the T tubules; release of Ca2+ from the sarcoplasmic reticulum (SR) (c) Action potential in the muscle membrane; splitting of adenosine triphosphate (ATP); binding of Ca2+ to troponin C The answer is b. The correct sequence is action potential in the muscle membrane; depolarization of the T tubules; release of Ca2+ from the sarcoplasmic reticulum (SR); binding of Ca2+ to troponin C; cross-bridge formation; and splitting of adenosine triphosphate (ATP). 16. In skeletal muscle, which of the following events occurs before depolarization of the T tubules in the mechanism of excitation– contraction coupling? (a) Depolarization of the sarcolemma membrane (b) Opening of Ca2+ release channels on the sarcoplasmic reticulum (SR) (c) Uptake of Ca2+ into the SR by Ca2+- adenosine triphosphatase (ATPase) (d) Binding of Ca2+ to troponin C (e) Binding of actin and myosin The answer is a. In the mechanism of excitation–contraction coupling, excitation always precedes contraction. Excitation refers to the electrical activation of the muscle cell, which begins with an action potential (depolarization) in the sarcolemma membrane that spreads to the T tubules. Depolarization of the T tubules then lead to the release of Ca2+ from the nearby sarcoplasmic reticulum (SR), followed by an increase in intracellular Ca2+ concentration, binding of Ca2+ to troponin C, and then contraction. 17. Which of the following is an inhibitory neurotransmitter in the central nervous system (CNS)? (a) Norepinephrine (b) Glutamate (c) γ-Aminobutyric acid (GABA) (d) Serotonin (e) Histamine The answer is C. γ-Aminobutyric acid (GABA) is an inhibitory neurotransmitter. Norepinephrine, glutamate, serotonin, and histamine are excitatory neurotransmitters. 18. Which of the following causes rigor in skeletal muscle? (a) Lack of action potentials in motoneurons (b) An increase in intracellular Ca2+ level (c) A decrease in intracellular Ca2+ level (d) An increase in adenosine triphosphate (ATP) level (e) A decrease in ATP level The answer is e. Rigor is a state of permanent contraction that occurs in skeletal muscle when adenosine triphosphate (ATP) levels are depleted. With no ATP bound, myosin remains attached to actin and the cross-bridge cycle cannot continue. If there were no action potentials in motoneurons, the muscle fibers they innervate would not contract at all, since action potentials are required for release of Ca2+ from the sarcoplasmic reticulum (SR). When intracellular Ca2+ concentration increases, Ca2+ binds troponin C, permitting the cross-bridge cycle to occur. Decreases in intracellular Ca2+ concentration cause relaxation. 19. Degeneration of dopaminergic neurons has been implicated in (a) schizophrenia (b) Parkinson disease (c) myasthenia gravis (d) curare poisoning The answer is b. Dopaminergic neurons and D2 receptors are deficient in people with Parkinson disease. Schizophrenia involves increased levels of D2 receptors. Myasthenia gravis and curare poisoning involve the neuromuscular junction, which uses acetylcholine (ACh) as a neurotransmitter. 20. A 56-year-old woman with severe muscle weakness is hospitalized. The only abnormality in her laboratory values is an elevated serum K+ concentration. The elevated serum K+ causes muscle weakness because (a) the resting membrane potential is hyperpolarized (b) the K+ equilibrium potential is hyperpolarized (c) the Na+ equilibrium potential is hyperpolarized (d) K+ channels are closed by depolarization (e) K+ channels are opened by depolarization (f) Na+ channels are closed by depolarization (g) Na+ channels are opened by depolarization The answer is F. Elevated serum K+ concentration causes depolarization of the K+ equilibrium potential and therefore depolarization of the resting membrane potential in skeletal muscle. Sustained depolarization closes the inactivation gates on Na+ channels and prevents the occurrence of action potentials in the muscle. 34. In contraction of gastrointestinal smooth muscle, which of the following events occurs after binding of Ca2+ to calmodulin? (a) Depolarization of the sarcolemma membrane (b) Ca2+-induced Ca2+ release (c) Increased myosin-light-chain kinase (d) Increased intracellular Ca2+ concentration (e) Opening of ligand-gated Ca2+ channels The answer is C. The steps that produce contraction in smooth muscle occur in the following order: various mechanisms that raise intracellular Ca2+ concentration, including depolarization of the sarcolemma membrane, which opens voltage-gated Ca2+ channels, and opening of ligand- gated Ca2+ channels; Ca2+-induced Ca2+ released from SR; increased intracellular Ca2+ concentration; binding of Ca2+ to calmodulin; increased myosin-light- chain kinase; phosphorylation of myosin; binding of myosin to actin; cross-bridge cycling, which produces contraction Autonomic nervous system (ANS) 1. Which autonomic receptor is blocked by hexamethonium at the ganglia, but not at the neuromuscular junction? (a) Adrenergic α receptors (b) Adrenergic β1 receptors (c) Adrenergic β2 receptors (d) Cholinergic muscarinic receptors (e) Cholinergic nicotinic receptors The answer is e. Hexamethonium is a nicotinic blocker, but it acts only at ganglionic (not neuromuscular junction) nicotinic receptors. This pharmacologic distinction emphasizes that nicotinic receptors at these two locations, although similar, are not identical. 2. A 66-year-old man with chronic hyper- tension is treated with prazosin by his physician. The treatment successfully decreases his blood pressure to within the normal range. What is the mechanism of the drug’s action? (a) Inhibition of β1 receptors in the sinoatrial (SA) node (b) Inhibition of β2 receptors in the SA node (c) Stimulation of muscarinic receptors in the SA node (d)Inhibition of α1 receptors on vascular smooth muscle The answer is d. Prazosin is a specific antagonist of α1 receptors, which are present in vascular smooth muscle, but not in the heart. Inhibition of α1 receptors results in vasodilation of the cutaneous and splanchnic vascular beds, decreased total peripheral resistance, and decreased blood pressure. 3. Which of the following is a feature of the sympathetic, but not the parasympathetic nervous system? (a) Ganglia located in the effector organs (b) Long preganglionic neurons (c) Preganglionic neurons release norepinephrine (d) Preganglionic neurons release acetylcholine (ACh) (e) Preganglionic neurons originate in the thoracolumbar spinal cord The answer is e. Sympathetic preganglionic neurons originate in spinal cord segments T1–L3. Thus, the designation is thoracolumbar. The sympathetic nervous system is further characterized by short preganglionic neurons that synapse in ganglia located in the paravertebral chain (not in the effector organs) and postganglionic neurons that release norepinephrine (not epinephrine). Common features of the sympathetic and parasympathetic nervous systems are preganglionic neurons that release acetylcholine (ACh) and postganglionic neurons that synapse in effector organs. 4. Which autonomic receptor mediates an increase in heart rate? (a) Adrenergic α receptors (b) Adrenergic β1 receptors  (c) Adrenergic β2 receptors (d) Cholinergic muscarinic receptors (e) Cholinergic nicotinic receptors The answer is B. Heart rate is increased by the stimulatory effect of norepinephrine on β1 receptors in the sinoatrial (SA) node. There are also sympathetic β1 receptors in the heart that regulate contractility. 5. Administration of which of the following drugs is contraindicated in a 10-year-old child with a history of asthma? (a) Albuterol (b) Epinephrine (c) Isoproterenol (d) Norepinephrine (e) Propranolol The answer is e. Asthma, a disease involving increased resistance of the upper airways, is treated by administering drugs that produce bronchiolar dilation (i.e., β2 agonists). β2 Agonists include isoproterenol, albuterol, epinephrine, and, to a lesser extent, norepinephrine. β2 Antagonists, such as propranolol, are strictly contraindicated because they cause constriction of the bronchioles. 6. Which adrenergic receptor produces its stimulatory effects by the formation of inositol 1,4,5-triphosphate (IP3) and an increase in intracellular [Ca2+]? (a) α1 Receptors (b) α2 Receptors (c) β1 Receptors (d) β2 Receptors (e) Muscarinic receptors (f) Nicotinic receptors The answer is A. Adrenergic α1 receptors produce physiologic actions by stimulating the formation of inositol 1,4,5-triphosphate (IP3) and causing a subsequent increase in intracellular [Ca2+]. Both β1 and β2 receptors act by stimulating adenylate cyclase and increasing the production of cyclic adenosine monophosphate (cAMP). α2 Receptors inhibit adenylate cyclase and decrease cAMP levels. Muscarinic and nicotinic receptors are cholinergic. 7. Which autonomic receptor mediates secretion of epinephrine by the adrenal medulla? (a) Adrenergic α receptors (b) Adrenergic β1 receptors (c) Adrenergic β2 receptors (d) Cholinergic muscarinic receptors (e) Cholinergic nicotinic receptors The answer is e. Preganglionic sympathetic fibers synapse on the chromaffin cells of the adrenal medulla at a nicotinic receptor. Epinephrine and, to a lesser extent, norepinephrine are released into the circulation.  8. Which of the following autonomic drugs acts by stimulating adenylate cyclase? (a) Atropine (b) Clonidine (c) Curare (d) Norepinephrine The answer is D. Among the autonomic drugs, only β1 and β2 adrenergic agonists act by stimulating adenylate cyclase. Norepinephrine is a β1 agonist. Atropine is a muscarinic cholinergic antagonist. Clonidine is an α2 adrenergic agonist. Curare is a nicotinic cholinergic antagonist. Phentolamine is an α1 adrenergic antagonist. Phenylephrine is an α1 adrenergic agonist. Propranolol is a β1 and β2 adrenergic antagonist. 9. Which autonomic receptor is activated by low concentrations of epinephrine released from the adrenal medulla and causes vasodilation? (a) Adrenergic α receptors (b) Adrenergic β1 receptors (c) Adrenergic β2 receptors (d) Cholinergic muscarinic receptors (e) Cholinergic nicotinic receptors The answer is c. β2 Receptors on vascular smooth muscle produce vasodilation. α Receptors on vascular smooth muscle produce vasoconstriction. Because β2 receptors are more sensitive to epinephrine than are α receptors, low doses of epinephrine produce vasodilation, and high doses produce vasoconstriction. 10. Sensory receptor potentials (a) are action potentials (b) always bring the membrane potential of a receptor cell toward threshold (c) always bring the membrane potential of a receptor cell away from threshold (d) are graded in size, depending on stimulus intensity (e) are all-or-none The answer is D. Receptor potentials are graded potentials that may bring the membrane potential of the receptor cell either toward (depolarizing) or away from (hyperpolarizing) threshold. Receptor potentials are not action potentials, although action potentials (which are all-or-none) may result if the membrane potential reaches threshold. Cardiac and Venous 1. An increase in contractility is demonstrated on a Frank-Starling diagram by (a) increased cardiac output for a given end- diastolic volume (b) increased cardiac output for a given end- systolic volume (c) decreased cardiac output for a given end-diastolic volume (d) decreased cardiac output for a given end-systolic volume The answer is a. An increase in contractility produces an increase in cardiac output for a given end-diastolic volume, or pressure. The Frank-Starling relationship demonstrates the matching of cardiac output (what leaves the heart) with venous return (what returns to the heart). An increase in contractility (positive inotropic effect) will shift the curve upward. 2. The greatest pressure decrease in the circulation occurs across the arterioles because (a) they have the greatest surface area (B) they have the greatest cross-sectional area (C) the velocity of blood flow through them is the highest (d) the velocity of blood flow through them is the lowest (e) they have the greatest resistance The answer is e. The decrease in pressure at any level of the cardiovascular system is caused by the resistance of the blood vessels (ΔP = Q × R). The greater the resistance is, the greater the decrease in pressure is. The arterioles are the site of highest resistance in the vasculature. The arterioles do not have the greatest surface area or cross-sectional area (the capillaries do). Velocity of blood flow is lowest in the capillaries, riot in the arterioles. 3. Pulse pressure is (a) the highest pressure measured in the arteries (b) the lowest pressure measured in the arteries (c) measured only during diastole (d) determined by stroke volume The answer is d. Pulse pressure is the difference between the highest (systolic) and lowest (diastolic) arterial pressures. It reflects the volume ejected by the left ventricle (stroke volume). Pulse pressure increases when the capacitance of the arteries decreases, such as with aging. 4. Myocardial contractility is best correlated with the intracellular concentration of (a) Na+ (b) K+ (c) Ca2+ (d) Cl– (e) Mg2+ The answer is C. Contractility of myocardial cells depends on the intracellular [Ca2+], which is regulated by Ca2+ entry across the cell membrane during the plateau of the action potential and by Ca2+ uptake into and release from the sarcoplasmic reticulum (SR). Ca2+ binds to troponin C and removes the inhibition of actin–myosin interaction, allowing contraction (shortening) to occur. 5. A 72-year-old woman, who is being treated with propranolol, finds that she cannot maintain her previous exercise routine. Her physician explains that the drug has reduced her cardiac output. Blockade of which receptor is responsible for the decrease in cardiac output? (a) α1 Receptors (b) β1 Receptors (c) β2 Receptors (d) Muscarinic receptors (e) Nicotinic receptors  The answer is B. Propranolol is an adrenergic antagonist that blocks both β1 and β2 receptors. When propranolol is administered to reduce cardiac output, it inhibits β1 receptors in the sinoatrial (SA) node (heart rate) and in ventricular muscle (contractility). 6. Propranolol has which of the following effects? (a) Decreases heart rate (b) Increases left ventricular ejection fraction (c) Increases stroke volume (d) Decreases splanchnic vascular resistance (e) Decreases cutaneous vascular resistance The answer is a. Propranolol, a β-adrenergic antagonist, blocks all sympathetic effects that are mediated by a β1 or β2 receptor. The sympathetic effect on the sinoatrial (SA) node is to increase heart rate via a β1 receptor; therefore, propranolol decreases heart rate. Ejection fraction reflects ventricular contractility, which is another effect of β1 receptors; thus, propranolol decreases contractility, ejection fraction, and stroke volume. Splanchnic and cutaneous resistance are mediated by α1 receptors. 7. Which receptor mediates slowing of the heart? (a) α1 Receptors (b) β1 Receptors (c) β2 Receptors (d) Muscarinic receptors The answer is d. Acetylcholine (ACh) causes slowing of the heart via muscarinic receptors in the sinoatrial (SA) node. 8. Which of the following agents or changes has a negative inotropic effect on the heart? (a) Increased heart rate (b) Sympathetic stimulation (c) Norepinephrine (d) Acetylcholine (ACh) (e) Cardiac glycosides The answer is d. A negative inotropic effect is one that decreases myocardial contractility. Contractility is the ability to develop tension at a fixed muscle length. Factors that decrease contractility are those that decrease the intracellular [Ca2+]. Increasing heart rate increases intracellular [Ca2+] because more Ca2+ ions enter the cell during the plateau of each action potential. Sympathetic stimulation and norepinephrine increase intracellular [Ca2+] by increasing entry during the plateau and increasing the storage of Ca2+ by the sarcoplasmic reticulum (SR) [for later release]. Cardiac glycosides increase intracellular [Ca2+] by inhibiting the Na+–K+ pump, thereby inhibiting Na+–Ca2+ exchange (a mechanism that pumps Ca2+ out of the cell). Acetylcholine (ACh) has a negative inotropic effect on the atria. 9. The low-resistance pathways between myocardial cells that allow for the spread of action potentials are the (a) gap junctions (b) T tubules (c) sarcoplasmic reticulum (SR) (d) intercalated disks (e) mitochondria The answer is a. The gap junctions occur at the intercalated disks between cells and are low-resistance sites of current spread.