MSF Exam Review Supplemental Instruction The MOORE you know! Special Situations Adrenals – no opposing action of parasympathetic system Vessels, sweat glands, piloerectors in head, - no opposing action of parasympathetic system Upper and lower extremities – no opposing action of parasympathetic system Liver - no opposing action of parasympathetic system Gallbladder - no opposing sympathetic system Special Situations Bladder function Fillingsympathetic dominates Sympathetic activation inhibits parasympathetic actions β-activation suppresses muscular contractions that cause bladder emptying α-activation controls closing of the internal sphincter Emptyingparasympathetic dominates Reduced sympathetic activation relieves inhibition of parasympathetic actions, relaxes internal sphincter Electrophysiology ● Electrochemical equilibrium → ○ ○ ○ ● Equal electrochemical potentials Based on both charge and concentration of the ion Larger electrochemical potential is where the ion moves Nernst – finds equilibrium potential/ voltage ○ Eion = - 60 mV log [ion]i z ● Conductance – finds RMP based on the ion’s equilibrium potential ○ ○ ● [ion]o Ratio of the conductance of ions vs. total conductance and the Nernst potential Shows the larger influence of K+ Goldman – determines RMP based on permeability and concentration Electrophysiology - RMP ● What determines the resting membrane potential (RMP)? ○ ○ ○ ○ ● “Ions try to drive the RMP to their potential” Established by the diffusion of Na+, K+, Cl-, Ca2+ Determined by conductance, differential membrane permeability, concentration (ion gradients), and ion potentials Na+/K+ ATPase is most important pump for contributing to the negative RMP within the cell Significance of hyperkalemia and hypokalemia on the RMP ○ Hyperkalemia = High K+ which depolarizes the RMP (closer to threshold) ○ Hypokalemia = Low K+ which hyperpolarizes the RMP Electrophysiology - Action Potential ● Ionic basis of each stage of the action potential → ○ RMP – few open channels ○ Upstroke – Na+ channels open (activation gate opens outside membrane) ○ Overshoot is when the membrane potential is positive ○ Repolarization – Na+ channels close (closing of inactivation channels inside membrane) and K+ channels remains open ○ Undershoot – K+ channels remain open and it approaches K+ equilibrium ■ ○ In order to prevent another signal unless very strong Refractory – membrane returns to RMP as voltage gated K+ channels are closed and Na+ channels return to resting state Electrophysiology - Action Potential ● Propagation of an action potential in a myelinated nerve axon → ○ ○ ○ ○ ○ Time constant (t) determined by membrane resistance and capacitance and determines how quickly a membrane depolarizes Length constant (λ) → current flows further with large diameter, high membrane resistance, and low internal resistance Conduction velocity (CV) → ■ Larger the diameter (lower resistance (Ri) & larger λ) = larger the velocity ■ Myelination increases the conduction velocity (CV) (increases membrane resistance and decreases capacitance) Leads to saltatory conduction in which the action potentials jump from a node of Ranvier to the next This prevents AP decay Muscle Physiology ● Functional anatomy of skeletal muscle → ○ ○ ○ 1 motor unit for innervation Sarcomere = z line to z line I band = thin filaments ■ ■ ■ Actin (Globular actin (G) forms into filamentous actin (F)) Tropomyosin run along the groove of the 2 actin chains Troponin is a globular protein (3 subunits) that binds to Tropomyosin (TNN_) ● ○ ○ ○ C = Calcium I = inhibitory A band = thick filaments [Myosin (2 heavy chains, 4 light chains, and globular head)] H band = bare zone (divided by M line) T-tubules and Sarcotubular system ■ ■ ■ ○ T = tropomyosin Triads of 2 terminal cisterns and 1 T tubule (part of sarcolemma membrane) (only in skeletal muscle) Important for Ca control T-tubule between A band and I band Cytoskeleton components ■ ■ ■ ■ Dystrophin – myofibrils to membrane Titin – thick filaments to z disk Nebulin – length of thin filament a-actin – thin filament to z disk Muscle Physiology ● Three types of skeletal muscle: ○ Type I (slow twitch) → no fatigue, red (myoglobin), oxidative metabolism, high mitochondria, low glycogen ○ Type IIa (fast) → no fatigue, red (myoglobin), oxidative metabolism, higher mitochondria, abundant glycogen ○ Type IIb (fast) → fatigue, white (low myoglobin), glycolytic metabolism, fewer mitochondria, high glycogen Muscle Physiology ● Functional anatomy of cardiac muscle → ○ Same contractile machinery w/ striations ○ Shorter myocytes ○ Intercalated disks → desmosomes linking cells mechanically and gap junctions electrically ○ More oxidative metabolism and mitochondria ○ Stimulation via SA node ○ a and B myosin heavy chain isoforms (aMHC in atria and BMHC in ventricles) ○ T-tubular system at Z line ● Functional anatomy of smooth muscle → ○ No troponin ○ Less extensive SR ○ Functional Pieces■ Actin, Myosin, Tropomyosin ■ Myosin light chain kinase; Myosin light chain phosphatase ■ Calmodulin ○ Stimulation via ANS through varicosities ○ Both multiunit (individual) and unitary (grouped) Cardiac Muscle Muscle Physiology ● Excitation-Contraction Coupling ○ Skeletal Muscle ○ ■ AP in sarcolemma → Depolarization of T tubule → Activate DHPR then RyR → Increase Ca2+ from SR → Ca2+ binds to TNNC → Conformational change in troponin and tropomyosin to uncover binding site ■ Cross bridge cycling and force generation: ● Rigor state → ATP binds to myosin head → Myosin released → ATP hydrolysis → Myosin binds and produces power stroke → ADP released Cardiac Muscle ■ ■ ■ ■ ■ No physical connection b/w DHPR and RyR DHPR brings Ca2+ into cell and RyR (ligand activated by Ca) removes it from SR Requires extracellular Ca2+ for AP Plateau phase of heart contraction means it is in absolute refractory period (no tetanus possible) Due to the influx of Ca2+ Muscle Physiology ● ● Excitation-Contraction Coupling Smooth Muscle ● Stimulus for Ca2+ entry into cell ● Increase in intracellular Ca2+ ● Binding of Ca2+ to calmodulin (four Ca2+ ions bind to calmodulin) ● Activation of myosin light chain kinase ● Phosphorylation of myosin light chain ● Increased myosin ATPase activity ● Myosin-actin binding and contraction ● Myosin light chain phosphatase dephosphorylates myosin ● Actin and myosin separated Muscle Physiology ● Length-tension and force-velocity relationships: ○ ○ ● Isometric → length stays same and tension increases ■ Max tension at length with most crossbridge activity ■ Studies preload Isotonic → weight stays same and length shortens ■ Velocity of shortening is highest at lowest load ■ Studies afterload Types of Action Potentials: ○ Spike (like skeletal), plateau (like cardiac), slow waves (like in gut) Muscle Physiology ● How muscle cells control their intracellular Ca2+ levels: ○ Skeletal→ ■ SERCA (Sarcoplasmic Endoplasmic Reticulum Ca2+ ATPase) (primary active transport) into SR ■ Calsequestrin and Calreticulin bind to free Ca in SR to keep free Ca concentration low and increase SERCA effectiveness ○ Cardiac→ ■ Same mechanism for removing Ca2+ ■ Ca2+ and Na+/Ca2+ ATPase more important ■ Extracellular Ca required for AP ○ Smooth→ ■ Extracellular Ca required for AP ■ Regulated by: ● Voltage-gated calcium channels in the sarcolemma ● Ligand-gated calcium channels in the sarcolemma ● Calcium-induced calcium release channels in the SR membrane ● IP3-induced calcium channels in the SR membrane What can cross the membrane? How are lipids distributed across the membrane? Membrane Fluidity and Cholesterol Modes of Cellular Communication MSF Exam Review Supplemental Instruction Let’s Ty it all together with some practice questions! In this course, physiology is defined as the study of biochemical, mechanical, and _____ functions that underlie life. A. Spiritual B. Cardinal C. Physical D. Mathematical You just drank a bottle of Gatorade. Your pancreatic beta cells begin to secrete insulin to drive serum glucose into the cells. As serum glucose decreases, your pancreatic beta cells stop secreting insulin. This is an example of what kind of feedback? A. Lateral feedback B. Positive feedback C. Transport maximum D. Negative feedback Cellular functions are integrated at the _____ level, and the organs systems are integrated at the level of the whole _____. A. Organ; organism B. Biochemical; cell Once equilibrium is reached, it’s not necessarily static. However, net movement/concentration remains virtually ______. A. forward B. unchanged C. opposite You can maintain a concentration gradient against physics by imparting _____. A. force B. energy C. mass D. torque In contrast to the somatic nervous system, the autonomic nervous system uses _____ A. a two efferent neuron chain B. a two afferent neuron chain C. no acetylcholine D. both afferent and efferent fibers equally Preparing the body for the “fight-or-flight” response is the role of the _____ A. sympathetic nervous system B. cerebrum C. parasympathetic nervous system D. somatic nervous system The parasympathetic nervous system is characterized by peripheral ganglia usually near the _____ A. spinal cord and by long postganglionic fibers B. spinal cord and by short postganglionic fibers C. organs and by short postganglionic fibers D. organs and by long postganglionic fibers Metoprolol is a β1 selective antagonist used to treat a variety of conditions. Given your knowledge on the sympathetic nervous system, what effect will this drug have on heart rate? A. Increase B. Decrease C. Elongate D. Asystole Over 90% of all parasympathetic fibers are derived from cranial nerve number ____. A. V B. VII C. IX D. X Which of these effectors is not directly controlled by the ANS? A. Smooth muscle B. Cardiac muscle C. Skeletal muscle D. Most glands Which of the following is not a result of parasympathetic stimulation? A. salivation B. dilation of the pupils C. increased peristalsis of the digestive tract D. elimination of urine The site of origin of the preganglionic fibers of the parasympathetic nervous system is the _____. A. Thoracolumbar region of the spinal cord B. Higher brain centers C. Sympathetic chain D. Craniosacral region Sympathetic responses generally are widespread because _____. A. Inactivation of Ach is fairly slow B. NE and epinephrine are secreted into the blood as part of the sympathetic response C. Preganglionic fibers are short D. Preganglionic fibers are long Which of the following characteristics is shared by simple and facilitated diffusion of glucose? A. B. C. D. E. Occurs down an electrochemical gradient Saturable Requires metabolic energy Inhibited by the presence of galactose Requires a sodium gradient During the upstroke of the nerve action potential: A. B. C. D. There is net outward current and the cell interior becomes more negative There is net outward current and the cell interior becomes less negative There is net inward current and the cell interior becomes more negative There is net inward current and the cell interior becomes less negative 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 calcium into the presynaptic nerve terminal B. Uptake of calcium into the presynaptic terminal, release of acetylcholine, depolarization of the muscle end plate C. Release of acetylcholine, action potential in the motor nerve, action potential in the muscle D. Uptake of calcium into the motor end plate, action potential in the motor end plate, action potential in the muscle E. Release of acetylcholine, action potential in the muscle end plate, action potential in the muscle The velocity of conduction of action potentials along a nerve will be increased by: A. B. C. D. E. Stimulating the sodium-potassium pump Inhibiting the sodium-potassium pump Decreasing the diameter of the nerve Myelinating the nerve Lengthening the nerve fiber A newly developed local anesthetic blocks sodium channels in nerves. Which of the following effects on the action potential would it be expected to produce? A. B. C. D. E. Decrease the rate of rise of the upstroke of the action potential Shorten the absolute refractory period Abolish the hyperpolarizing afterpotential Increase the sodium equilibrium potential Decrease the sodium equilibrium potential Which of the following cytoskeletal components anchor thick filaments to Z disk? A. B. C. D. E. Nebulin Titin Dystrophin Alpha-actinin Myosin Which of the following sequences is the correct order of excitation-contraction coupling in skeletal muscle? A. Action potential in muscle membrane, depolarization along T tubules, power stroke producing contraction, intracellular calcium concentration increased after release from the SR, calcium binds to troponin C, formation of cross-linkages between thin and thick filaments B. Calcium binds troponin C, depolarization along T tubules, action potential in muscle membrane, exposure of myosin binding site on actin, formation of cross-linkages between thin and thick filaments, power stroke producing contraction C. Action potential in muscle membrane, depolarization along T tubules, intracellular calcium concentration rises after being released from the SR, calcium binds troponin C, exposure of myosin binding site on actin, formation of cross-linkages between thin and thick filaments, power stroke producing contraction D. Intracelluar calcium concentration rises after being released from the SR, calcium binds troponin C, action potential in muscle membrane, depolarization along T tubules, formation of cross-linkages between thin and thick filaments, power stroke producing contraction Which skeletal muscle fiber type is referred to as slow twitch? A. B. C. D. E. Type IIA Type IIB Type III Type I Type IV Which skeletal muscle fibers are primarily being used when someone is running a marathon? A. B. C. D. E. Type I Type IIA Type IIB Type III Type IV Describe the role of calsequestrin. A. B. C. D. E. Calcium binding protein in the SR to reduce free calcium concentration Actively transports calcium back into the SR Channel in the plasma membrane responsible for Na-Ca exchange Channel in the SR used to increase Ca concentration in the cytosol I don’t know Ty, it’s still week 1 In skeletal muscle, which of the following events occurs before depolarization of the T tubules in the mechanism of excitation-contraction coupling? A. B. C. D. E. Depolarization of the sarcolemmal membrane Opening of calcium release channels on the SR Uptake of calcium into the SR by calcium-ATPase Binding of calcium to troponin C Binding of actin and myosin Where is the ryanodine receptor located, and what is its role? A. Plasma membrane; channel that allows calcium to move intracellularly for muscle contraction B. Sarcoplasmic reticulum; ligand sensitive channel responsible for the release of calcium from the SR into the cytosol C. Sarcoplasmic reticulum; calcium binding protein in the SR to reduce free calcium concentration D. Cytosol; receptor on troponin C that calcium binds to directly to begin muscle contraction Why does tetanus not occur in cardiac muscle like it may in skeletal muscle? A. The heart is the best B. Cardiac muscle is under relative refractory period during the plateau phase in which it cannot be stimulated C. Cardiac muscle is under absolute refractory period during the plateau phase in which it cannot be stimulated D. There is not enough calcium in cardiac muscle to be concerned E. Cardiac muscle has very slow action potentials making tetanus nearly impossible What is the role of intercalated disks in cardiac muscle? A. Stops calcium from spreading to too many cells B. Plays fun music that the heart keeps beating to C. Structure that anchors cardiac myocytes to one another to share various nutrients D. Structure that anchors cardiac myocytes to one another to propagate action potentials E. Location of muscle fibers in cardiac muscle What electrolyte is responsible for the prolonged plateau phase in cardiac muscle? A. B. C. D. E. ClK+ Ca2+ Na+ Mg2+ What is the intracellular calcium sensor in smooth muscle for contraction to occur? A. B. C. D. E. Myosin light chain kinase Calmodulin Myosin Troponin Myosin light chain phosphatase Describe myosin light chain phosphatase role in smooth muscle contraction. A. B. C. D. Terminates muscle contraction Phosphorylates myosin light chains Phosphorylates myosin to bind to actin to form cross bridge Removes phosphate from actin In contraction of gastrointestinal smooth muscle, which of the following events occurs after binding of calcium to calmodulin? A. B. C. D. E. Depolarization of the sarcolemmal membrane Calcium induced calcium release Increased myosin light chain kinase Increased intracellular calcium concentration Opening of ligand gated calcium channels Which characteristic or component is shared by skeletal muscle and smooth muscle? A. B. C. D. E. Thick and thin filaments arranged in sarcomeres Troponin Elevation of intracellular calcium for excitation-contraction coupling Spontaneous depolarization of the membrane potential High degree of electrical coupling between cells Fever can be reduced by inhibiting what enzyme? A. B. C. D. E. GTPase ATPase Carbonic anhydrase Cyclooxygenase Phosphodiesterase The heat dissipating mechanism caused by air currents is considered which of the following? A. B. C. D. E. Convection Conduction Radiation Sweating Evaporation Which second messenger is associated with protein kinase A? A. B. C. D. E. Nitric oxide cAMP CGMP Calcium Leukotrienes Which of the following is an example of juxtacrine signaling? A. B. C. D. E. The hormone vasopressin binding to its membrane receptor in the kidney The neurotransmitter serotonin binding to its membrane receptor in the small intestine The paracrine histamine binding to its receptor in the stomach The gap junctions connecting cardiac myocytes during muscle contraction The hormone testosterone binding to the MR receptor in the liver How many transmembrane regions does a GPCR contain? A. B. C. D. E. Four Five Six Seven Eight Which component contains GTPase activity? A. B. C. D. E. Ligand-gated ion channel activated by acetylcholine The beta-subunit of the G protein The beta,gamma-subunit of the G protein The alpha-subunit of the G protein The glycosylated portion of the catalytic receptor