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Test Details:
1) 2) 3) 4)
Approx. 3 questions per lecture 1.2 minutes per question Department practice exam on Blackboard TLEs on M1 website (go to: Class Materials then Physiology)
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Membranes
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Phospholipid bilayer with proteins and cholesterol embedded within bilayer. Cholesterol makes bilayer stiffer or more viscous!! Membrane composition depends on function (ie. More lipid in Schwann cells and more protein in mitochondria).
Intrinsic proteins span the entire membrane and contain hydrophillic ends and a hydrophobic core, often serving as transporters. Extrinsic proteins are present on one side of the bilayer or the other and are anchored by electrostatic interactions. Glycolipids can be conjugated with either an intrinsic or extrinsic protein and serve as a surface marker for the cell.
Transport
1) Simple Diffusion - small, nonpolar > large, polar 2) Osmosis - water follows solute 3) Facilitated Diffusion - not energy dependent transport of solute down its concentration gradient 4) Active Transport - energy dependent transport of solute against its concentration gradient
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Note: All transport mechanisms exhibit saturation kinetics, chemical specificity and competitive inhibition. When the [substrate] increases, the transportation rate increases until transport mechanism becomes saturated.
Transport
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Diffusion
DC J = - DA DX
Stokes-Einstein Equation:
Partition Coefficient ( )
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Lipid solubility ( ) - the more lipid soluble, the faster the diffusion. C - the greater the change in concentration, the faster the diffusion. Membrane thickness - the thinner the membrane, the faster the diffusion. Viscosity of membrane - the less viscous the membrane, the faster the diffusion. Radius of molecule - the smaller the radius of the molecule, the faster the diffusion.
Osmosis
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Use to calculate osmotic pressure = pressure required to oppose the movement of water from an area of high [H2O] (low osmolarity) to an area of low [H2O] (high osmolarity). Vw=L Use to calculate the osmotic flow rate of water when the membrane is permeable to both water and solute. = reflection coefficient (0-1) - a high reflection coefficient reflects a solute that does NOT permeate the membrane well.
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Hypotonic solutions have a lower osmolarity than cellular osmolarity (0.3 osm) and thus the cell will swell when placed in a hypotonic solution.
Hypertonic solutions have a higher osmolarity than cellular osmolarity and thus the cell will shrink when placed in a hypertonic solution.
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Facilitated Diffusion
Helps larger, less soluble molecules cross
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Active Transport
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Active Transport
Transporter is indirectly dependent on energy expenditure from another transporter ex. Na/glucose co-transporter fueled by Na+/K+ pump
NOTE: Na+/K+ pump = PumpKin (Pump K+ in)
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Gated Channels
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Membrane Potentials
Results because of an unequal distribution of charge across a membrane Two equations you need to know:
1) 2)
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Nernst Equation:
- 60 mV E = z
[ X ]A log + [X ]
B
Use to calculate the membrane potential of an ion at equilibrium Represents the electrical potential necessary to maintain a certain concentration gradient of a permeable solute.
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Goldmans Equation
Used to calculate overall membrane potential when multiple ions are involved. Incorporates permeability of each ion. Permeability of K+ > Na+ > Cl- thus..
Neurotransmitters
Acetylcholine (ACh)
Somatic NS
At neuromuscular junction
Autonomic NS
Preganglionic PNS and SNS neurons Postganglionic PNS
Norepinephrine
ANS- postganglionic SNS neurons Inhibitory neurotransmitter of brain Excitatory neurotransmitter of brain
GABA
Glutamate
Receptors
Binding activates Gprotein which activates and enzyme serving as a 2nd messenger
mACh receptors
Must bind glycine to be active Ligand gated Na, K and Ca channels blocked by Mg at rest
1, 2, 1, 2, and 3
SNS Receptors
Pro-PNS Effects
Pro-SNS Effects
APs are the result of time and voltage dependent changes in ionic permeability of excitable cells (i.e. neurons). Na+ and K+ channels that generate APs are only found at the axon hillock. Any other depolarization in a neuron is called a receptor potential. APs are ALL-OR-NOTHING events. A stronger stimulus only increases the frequency of firing.
3.
4. 5.
Slow depolarization to threshold Rapid depolarization due to opening of voltage dependent Na+ channels leading to Na+ influx (Hodgkin Cycle!) Repolarization due to increased K+ conductance leading to K+ efflux Hyperpolarization (refractory period) Resting membrane potential
Refractory Periods
No amount of inward current will generate another AP Due to the Na+ inactivation gate which is slow to close when triggered at threshold
Need an excess of current to generate an AP because the Na+ channels are still inactivated until the end of repolarization phase
Velocity of Conduction of AP
Velocity increases
Velocity increases
Synaptic Transmission
Presynaptic Membrane:
AP Ca+2 channels opening Ca+2 influx synaptic vesicle fusion release of NTs
Post-synaptic membrane: Neurotransmitter binds to postsynaptic neuron or muscle leading to increased conductance of Na+ and K+ causing a generator or action potential.
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Response may be inhibitory or excitatory depending on the nature of postsynaptic cell (NOT Neurotransmitter!!) Temporal or Spatial Summation Temporal - multiple signals from 1 axon firing in rapid succession such that successive inputs add to the stillexistent present inputs. Spatial - multiple signals from different axons occurring simultaneously. Repetitive Stimulations Facilitation - successive APs cause postsynaptic membrane potential to grow more and more intense in amplification Post-tetanic Potentiation - after repetitive firing, Ca+2 channels are synchronized resulting in a more amplified EPSP following tetanus Synaptic Fatigue - delay in response after synapse following prolonged tetanus (NTs have to be re-packaged)
Generator Potentials
Action Potentials
Over threshold All or Nothing!!! Intensity of signal = more frequent Aps No decrement in signal
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Somatic NS
Autonomic NS
Acts on skeletal muscles 1 neuron ACh nACh (motor end plate) Controlled by voluntary thought (motor cortex)
Acts on smooth muscle, glands, cardiac muscle 2 neurons: post and preganglionic PreG: ACh nACh Post G:
PNS: ACh mACh SNS: NE or
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Autonomic NS
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Sympathetic
Cell bodies of postganglionic nerves are in ganglia near spinal cord Diffuse control (1:10 ratio of pre to postG fibers) Short preganglionic nerves (ACh nACh receptors) Long post ganglionic nerves (NE 1, 2, 1 and 2)
Parasympathetic
Cell bodies of postganglionic nerves are in ganglia near organ Precise control (1:3 ratio of pre to postG fibers) Long preganglionic nerves (ACh nACh receptors) Short postganglionic nerves (ACh mACh receptors)
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Dilates pupils Opens airways Increases heart rate and BP Increases blood flow to heart, brain and skeletal muscle Inhibits digestion Piloerection Gluconeogenesis and glycogenolysis (makes glucose available)
Constricts pupils Restricts airways Decreases heart rate and BP Promotes digestion Increases blood flow to gut Increase saliva Glyconeogenesis (stores glucose as glycogen)
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Salivary Secretions:
SNS: salivary amylase production PNS: watery saliva SNS: motility of colon until appropriate time PNS: motility of colon leads to expulsion of stool SNS: Relaxation of bladder to allow for fill-up PNS: Contraction of bladder SNS: Ejaculation and psychogenic erections PNS: Erection (ACh NO release vasodilation)
Defecation
Urination
Erection
Muscle
Skeletal Muscle
Controlled by Somatic NS Skeletal muscle specific terms:
Neuromuscular junction Motor endplate skeletal muscle on the receiving end of nm junction End Plate Potential (EPP) generator potential of skeletal muscle
Classification of Muscle
Functional Syncytium Cardiac Automaticity Single-Unit
Striated Muscle
Motor Unit Composition Skeletal Motor Nerve Required Multi-Unit
Smooth Muscle
Epimysium
surrounds entire muscle separates muscle into bundles of muscle fibers (fascicles) contains blood vessels separates muscle fascicles into individual muscle cells (myofibers) contains capillaries
Perimysium
Endomysium
Epimysium, perimysium, and endomysium all come together at the ends of muscles to form TENDONS
Anatomy of a Muscle
Nerves and blood vessels are embedded in connective tissue. The major connective tissue components are collagen and elastin. Muscles are attached to bones by tendons at their origin and insertion.
Cell Fusion
Myofibers
The Sarcomere
Basic Contractile Unit in Muscle
M line
Myofilament Arrangements
A cross-section through the A Band/I Band overlap shows the hexagonal array of thick and thin myofilaments
When muscle contracts, the sarcomere shortens. The I band and H Zone also shorten. But the length of the A band remains the same.
The thick myofilaments are composed of myosin molecules arranged in an end to end fashion at the M-line. Each myosin is composed of two myosin heavy chain subunits and two pair of myosin light chains.
Thin myofilaments
Troponin
T attaches troponin complex to tropomyosin I along with tropomyosin inhibits myosin binding site on actin C binds free intracellular calcium to produce a conformational change in tropomyosin
Titin
keeps thick myofilaments centered in sarcomere extends from M line to Z line, largest MW protein known determines length of thin myofilaments, molecular ruler
Nebulin
filament structure during contraction Cap-Z and tropomodulin associated with opposite ends of growing thin filaments, regulates length Dystrophin anchors actin filaments to sarcolemma, defective in MD Myotilin interacts with alpha actinin and Z-lines, sarcomeric organization
Alpha Actinin anchors thin myofilaments to the Z-line Beta Actinin determines length of thin filaments Myomesin binds titin, aligns thick filaments into hexagonal array Desmin cytoskeletal protein, connects adjacent sarcomeres C-, H-, and X- proteins form rings around thick filaments, maintains thick
Some definitions
Motor Unit
Composed of an alpha motorneuron and all the myofibers innervated by that neuron The region of the myofiber directly under the terminal axon branches Where the axon terminal and the motor endplate meet
Motor Endplate
Neuromuscular junction
Spinal chord
Type II
Type I
Acetylcholine receptor
Excitation-Contraction Coupling
Resting Muscle
No at resting membrane potential
RyR Receptor
_ _
Ca++ Ca++
DHP Receptor
++
Ca++ Calsequestrin
Ca++ Ca++
Ca++ Ca++
Ca++ Ca++
Ca++
ATP
SR-Ca++ ATPase
Excitation-Contraction Coupling
Contracting Muscle
Depolarized
RyR Receptor
+ +
Ca++ Ca++
DHP Receptor
++
Ca++
Ca++
Ca++ Ca++
Ca++
Ca++
Ca
+ +
ATP
SR-Ca++ ATPase
Crossbridge Formation
Sarcomeric Shortening
Excitation-Contraction Coupling
Relaxing Muscle
No at resting membrane potential
RyR Receptor
_ _
Ca++ Ca++
DHP Receptor
++
Ca++ Calsequestrin Ca
Ca++ Ca++
+ +
Ca++
Ca++ Ca++
Ca++
Ca++ ADP + Pi
SR-Ca++ ATPase
Ca2
A + M ADP Pi
(Ca edIn ed te) h rg term ia
Crossbridge attachment
A M ATP
Crossbridge detachment
3
A M ADP Pi
Crossbrige Motion
ATP
A M
Rigor mortis if no ATP
ADP + Pi
Crossbridge Motion
Changes in the conformation of the hinge region of the myosin molecule allow for swivel motion of the crossbridges that produces sarcomeric shortening.
Describes the mechanism of muscle contraction Free energy from cleavage of Mg*ATP induces a bend in myosin head from a 90 to 45 degree angle Actin filaments slide toward the H zone, pulling the Z lines inward Sarcomere shortens and muscle contracts This happens in a wave - not synchronous for each sarcomere
Sample Question #1
Lengths at rest: A band = 1.5 m I band = 1.0 m H zone = 0.7 m What is the length of the a) sarcomere? b) thin filament? c) overlap?
Sample Question #1
Lengths at rest: A band = 1.5 m I band = 1.0 m H zone = 0.7 m What is the length of the a) sarcomere? 1.5 + 1.0 = 2.5 m b) thin filament? (2.5 0.7) / 2 = 0.9 m c) overlap? 1.5 0.7 = 0.8 m
Sample Question #2
Lengths at rest: A band = 1.5 m I band = 1.0 m H zone = 0.7 m Sarcomere = 2.5 m During contraction, the muscle shortens by 20%. What is the length of the a) sarcomere? b) thick filament? c) I band? d) H zone? e) overlap?
Sample Question #2
Lengths at rest: A band = 1.5 m I band = 1.0 m H zone = 0.7 m Sarcomere = 2.5 m During contraction, the muscle shortens by 20%. What is the length of the a) sarcomere? b) thick filament? c) I band? d) H zone? e) overlap? 2.5 0.5 = 2.0 m 1.5 m (no change!) 2.0 1.5 = 0.5 m 2.0 [(2) x (0.9)] = 0.2 m 1.5 0.2 = 1.3 m
Generation of tension in a muscle depends on its initial length Maximal tension can be developed at a sarcomeres optimal length, usually its resting length At the optimal length, a maximum number of crossbridge sites are accessible to the actin molecules for binding and bending When a muscle is passively stretched, the thin filaments are pulled out and there are less actin sites available for cross-bridge binding, decreasing tension When a muscle is shorter than its optimal length, tension decreases because the thin filaments overlap and the thick filaments become forced against the Z-lines
Active State
Describes criteria which must be met for contraction to occur: a) binding of calcium to troponin C b) cross-bridge formation c) ATP splitting d) cross-bridge motion
Action potential
Summation
Muscle force can be modulated by the frequency of stimulation Depends on active state and refractory period Skeletal muscle exhibits a long active state and a short refractory period Allows a second action potential long before the initial twitch response is complete Subsequent twitches build upon the one before, ultimately achieving a tetanus state
Summation of Twitches
The force of muscle contraction can be increased by increasing the frequency of nerve stimulation. The key is the difference in the time course for the action potential, calcium transient, and mechanical response.
Onset of Fatigue
1/sec
5/sec
10/sec
50/sec
Stimulation at low frequencies produces summation of twitches and tetanus. However, when stimulation frequency reaches a rate rapid enough to produce a complete tetanus, fatigue will develop. Fatigue in tetany is due to fast twitch muscles
Muscle Architecture
Force production and velocity of shortening of the whole muscle depends on the architecture. It is important to remember that force is proportional to myofiber number, while velocity is proportional to myofiber length. Therefore, strap-like muscles provide the greatest velocity of shortening, while pennate muscles can generate more force.
Leverage
Because muscles operate across joints, the force applied to move an object depends on the leverage factor LF = Leverage arm / Distance from joint The farther away from the joint a muscle is inserted, the smaller the leverage factor and the easier it is to move an object (example: door hinge) The closer a muscle is inserted to the joint, the larger the leverage factor (mechanical disadvantage), but the more maneuverable the object is
Extent of Shortening
Preloaded with 10 kg
Afterloaded with 10 kg
Action Potential Muscle Twitch
The latent period is prolonged in an afterloaded muscle because it takes time to stretch the series elastic component. The length of the latent period is dependent on load for afterloaded muscle, but independent of load for preloaded muscle. Increasing load decreases twitch shortening independent of effects on latent period.
Extent of Shortening
Action Potential
Muscle Twitch
Extent of Shortening
Preloaded with 20 kg
Afterloaded with 20 kg
Action Potential Muscle Twitch
Load-Velocity Relationship
Sample Question #3
A muscle which weighs 12 g and is 100 cm long is stimulated for a total of one hour at a frequency of 4/min. Upon each stimulation the muscle lifts 204 g and shortens 0.5 meters. What is the work and power output of that muscle?
Sample Question #3
A muscle which weighs 12 g and is 100 cm long is stimulated for a total of one hour at a frequency of 4/min. Upon each stimulation the muscle lifts 204 g and shortens 0.5 meters. What is the work and power output per hour of that muscle?
Force produced per stimulation = 0.204 kg x 9.81 m/s2 = 2.00124 N Work done during 1 contraction = 2 N x 0.5 m = 1.0 Joules Work done per hour = 1.0 J x 4/min x 60 min = 240 J Power output over 1 hour = 240 J / 3600 sec = 0.067 Watts Total work per gram of muscle = 240 J / 12 g = 20.0 J/g
Anaerobic Glycolysis
Aerobic Mechanisms
Creatine Phosphate
10 sec. 30 sec.
2 min.
5 min.
Exercise Duration
Performance Profile
MHC-ATPase Twitch Speed
High
Oxidative Activity
Low
IIB
Fast Twitch Red Moderate V. High High High Sustained phasic
IIA
Slow Twitch Low Moderate Low V. High Sustained Tonic
The activity profile of the major muscle fiber types matches the biochemical and contractile profiles for these fiber types.
Anaerobic Threshold
60
Oxygen Consumption
100 80
(ml/kg/min)
45 60
Anaerobic Threshold
30
Untrained Trained
40 20
REST
Oxygen Debt
oxygen debt and oxygen repayment are equal
Oxygen Debt
Oxygen Consumption
Oxygen Repayment
Time (minutes)
Training
De-training
Capillary Density
12
24
Time (months)
Efficiency Calculations
A 70-kg individual does 20 pullups, lifting his body weight 1 meter each time. In doing so, he consumes 4 liters of O2. Baseline is 400 ml of O2/min. Total exercise time is 5 mins. What is his gross and net mechanical efficiency. 1 L O2 = 4.8 kcal 1 cal = 4.186 J
Efficiency Calculations
A 70-kg individual does 20 pullups, lifting his body weight 1 meter each time. In doing so, he consumes 4 liters of O2. Baseline is 400 ml of O2/min. Total exercise time is 5 mins. What is his gross and net mechanical efficiency. 1 L O2 = 4.8 kcal 1 cal = 4.186 J W = mgh = (70 x 9.8 x 1) x 20 reps = 13.7 kJ = 13.7 kJ/4.186 kJ/kcal = 3.3 kcal
Efficiency Calculations
A 70-kg individual does 20 pullups, lifting his body weight 1 meter each time. In doing so, he consumes 4 liters of O2. Baseline is 400 ml of O2/min. Total exercise time is 5 mins. What is his gross and net mechanical efficiency. 1 L O2 = 4.8 kcal 1 cal = 4.186 J W = mgh = (70 x 9.8 x 1) x 20 reps = 13.7 kJ = 13.7 kJ/4.186 kJ/kcal = 3.3 kcal Total E = 4 L x 4.8 kcal = 19.2 kcal Net E = (4 L 0.4 L x 5 min) x 4.8 kcal = 9.6 kcal
Efficiency Calculations
A 70-kg individual does 20 pullups, lifting his body weight 1 meter each time. In doing so, he consumes 4 liters of O2. Baseline is 400 ml of O2/min. Total exercise time is 5 mins. What is his gross and net mechanical efficiency. 1 L O2 = 4.8 kcal 1 cal = 4.186 J W = mgh = (70 x 9.8 x 1) x 20 reps = 13.7 kJ = 13.7 kJ/4.186 kJ/kcal = 3.3 kcal Total E = 4 L x 4.8 kcal = 19.2 kcal Net E = (4 L 0.4 L x 5 min) x 4.8 kcal = 9.6 kcal Gross Efficiency = W/E = 3.3 kcal/19.2 kcal = 17% Net Efficiency = 3.3/9.6 = 34%
Fiber Types
Metabolism White Fast Slow Red Fast Red Glycolysis Oxidative Oxid/Glyc ATPase Fatigue Contraction activity Resistance + Short term phasic ++ Sustained tonic + + Sustained phasic Adaptation hypertrophy Incr mt myoglobin both Example Power lift Postural mm rowing
Present in GI tract, bladder, uterus, and ureter Contracts in coordinated fashion b/c of gap jxns Modulated by NTs and hormones Has pacemaker activity, slow waves
Found in iris, ciliary muscels of lens, and the vas deferens Cells dont communicate w/ each other electrically Densely innervated by autonomics
1) Action potential opens Ca2+ channels in sacrolemmal membrane 2) Rise in intracellular Ca2+ concentration causes Ca2+ bind to calmodulin the Ca2+ - Calmodulin complex binds to and activates myosin light chain kinase(MLCK) 3) Activated MLCK phosphorylates myosin, which can now form an break cross-bridges *amount of cross-bridges=tension=intracellular Ca2+ 4) Intracellular Ca2+ decreases(b/c of SRs Ca2+ ATPase) and myosin is dephosphorylated by myosin light chain phosphatase(MLCP)
Action potential, calcium release, depolarization of the t-tubules, contraction, calcium re-uptake Action potential, depolarization of the t-tubules, calcium release, contraction, calcium re-uptake Action potential, depolarization of the t-tubules, calcium re-uptake, contraction, calcium release Action potential, calcium release, contraction, depolarization of the t-tubules, calcium re-uptake
b)
c)
d)
Action potential, calcium release, depolarization of the t-tubules, contraction, calcium re-uptake Action potential, depolarization of the t-tubules, calcium release, contraction, calcium re-uptake Action potential, depolarization of the t-tubules, calcium re-uptake, contraction, calcium release Action potential, calcium release, contraction, depolarization of the t-tubules, calcium re-uptake
b)
c)
d)
At equilibrium the concentration of Na + is 5 mM inside the cell and 500 mM outside the cell. What is the Na + equilibrium potential for this cell?
a) b) c) d) e)
At equilibrium the concentration of Na + is 5 mM inside the cell and 500 mM outside the cell. What is the Na + equilibrium potential for this cell?
a) b) c) d) e)
According to the "size principle" which of the following statements would be true?
a) b) c) d) e)
large motor units are recruited first but generate less force large motor units are recruited first and generate more force small motor units are recruited first and generate more force small motor units are recruited first but generate less force motor unit size and force production are not related so none of the above are true.
According to the "size principle" which of the following statements would be true?
a) b) c) d) e)
large motor units are recruited first but generate less force large motor units are recruited first and generate more force small motor units are recruited first and generate more force small motor units are recruited first but generate less force motor unit size and force production are not related so none of the above are true.
According to the sliding filament theory, which of the following occurs during a muscle contraction:
a)
The thin filaments pull the H zone to the center of the sarcomere. The Z lines pull the thick filaments in the overlapping region. The area of overlap between the thick and thin filaments increases, however the actual lengths of the thick and the thin filaments remain unchanged. The width of both the I band and the A band decreases while the H zone increases.
b) c)
d)
According to the sliding filament theory, which of the following occurs during a muscle contraction:
a)
The thin filaments pull the H zone to the center of the sarcomere. The Z lines pull the thick filaments in the overlapping region. The area of overlap between the thick and thin filaments increases, however the actual lengths of the thick and the thin filaments remain unchanged. The width of both the I band and the A band decreases while the H zone increases.
b) c)
d)
shivering. increased pulmonary circulation. piloerection. increased cutaneous circulation. increased mesenteric circulation.
shivering. increased pulmonary circulation. piloerection. increased cutaneous circulation. increased mesenteric circulation.
Which of the following features are the same in the sympathetic and parasympathetic nervous system?
a) b) c) d)
Average length of preganglionic fibers. Average length of postganglionic fibers. Neurotransmitter in preganglionic fibers. Neurotransmitter in postganglionic fibers.
Which of the following features are the same in the sympathetic and parasympathetic nervous system?
a) b) c) d)
Average length of preganglionic fibers. Average length of postganglionic fibers. Neurotransmitter in preganglionic fibers. Neurotransmitter in postganglionic fibers.
The following data are given for a skeletal muscle fiber: Length of thin filament: 0.8um Length of H-zone: 0.4um The muscle is stimulated under isotonic conditions and it shortens 20%. What is the approximate length of the sarcomere in the contracted muscle according to the sliding filament theory?
a) b) c) d) e)
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The following data are given for a skeletal muscle fiber: Length of thin filament: 0.8um Length of H-zone: 0.4um The muscle is stimulated under isotonic conditions and it shortens 20%. What is the approximate length of the sarcomere in the contracted muscle according to the sliding filament theory?
a) b) c) d) e)
GOOD LUCK!!