Skeletal and smooth muscle Flashcards
Individuals with prolonged immobilization experience atrophy of what type of muscle fibers?
Atrophy of type I fibers (slow twitch) and reduced diamter of type II fibers
At the same time capillary density in the immobilized muscles will decline
What detects the length of stretch or shortening in muscle?
Muscle spindles detect length of stretch (or shortening) as well as the velocity of contraction
Golgi tendon organs
Sense the force generated by a muscle gaugin the tension developed in muscle tension
X-linked muscular dystrophy
Duchenne’s muscular dystrophy
Skeletal muscle is replaced by adipose tissue
X-linked recessive - affects boys>girls
LOF mutation - deletion of gene that codes for dystrophin (largest gene in the human genome - highest risk of error)
Dystrophin- cell membrane protein that allows for interaction of the muscle fiber with extracellular matrix.
Disease is progressive, from proximal skeletal muscle outward toward the distal muscles
Presents around 1 y/o - affects quadriceps first (difficulty walking)
Total paryalysis by second decade of life - death occurs as result of myocardial infiltration
Gower’s sign
The unusual way in which a child w/ x-linked muscular dystrophy will use a series of hand pushes to rise from the ground - unable to rely on hip flexors or shoulder muscles
Becker’s muscular dystrophy
Same disease as Duchenne’s except there’s a mutation of the dystrophin gene rather than a deletion
Because there is some protein as opposed to none - disease is often milder
Myasthenia gravis
Autoimmune disorder caused by antibodies against postsynaptic nicotinic ACh receptors - binding of Ab’s competively inhibits ACh from binding
Decaying force of contraction on rapidly repeated contractions
Small muscles and muscles that are used a lot are affected most
Pt’s will c/o blurry bision, dysphagia, and difficulty writing
Pt’s with MG can sometimes have a hyperproliferation of mediastinal thymic tissue (thymom) - removal can reverse sxs of MG
Myasthenia gravis vs. Lamber-Eaton syndrome
Diagram
Lambert-Eaton Myasthenic Syndrome
More than 1/2 cases are associated w/ small cell lung cancer - Tx’ing the cancer helps resolve the sxs
Due to antibodies against voltage-gated calcium channels on presynaptic nerve terminals leading to a decrease in ateylcholine release
W/ successive presynaptic action potneitlas that temporally sum, ACh will be released and contraction will occur. Increasing frequency of contraction increases the strength of contraction - muscles not often used are first affected
myotonias
Are conditions characterized by the impairment of muscle relaxation following voluntary contraction or electrical stimkulation.
One sign is the inability to loosen a handgrip after lifting a heavy object or after a handshake
Myotonic dystrophy 1
Results from synthesis of a defective RNA that sequesters RNA binding proteins causing dysregulated RNA splicing. This leads to down regulation of a voltage-gated Cl channel (ClC1) involved in stabilizing muscle cell membrane potentials
Fx loss of this ClC1 leads to myotonia
Congenital myotonia
Results from a defect in the CLCN1 gene - encodes for ClC1 protein
TN fainting goats - result from a mutation in CLCN1
Malignant hyperthermia (MH)
Hereditary disorder of skeletal muscle - hypermetabolic response to halogenated anesthetic gasses and/or depolarizing muscle relaxant succinylcholine
Mutation in the ryanodine receptor results in uncontrolled release of calcium from skeletal muscle SR leading to sustained muscle contraction.
Dantrolene inhibits the ryanodine receptor calcium release channel in skeletal muscle without affecting nueromuscular transmission and is effective for both prophylaxis and tx of active MH
Myofilament composition
Myosin 2 and actin - make up the contractile unit (sarcomere)
Myosin vs actin on ESM
Myosin - appear darker than actin on an electron micrograph
Areas of overlap between myosin and actin appear darkest of all
Zones/bands of the sarcomere
During contraction which lines of the sarcomere get closer together?
The Z lines get closer together
During muscle contraction, what organelle propagates the action potential?
The T-tubule
Depolarization activates and opens the gate of T-tubule voltage-gated L-type calcium channels - do not allow for sufficient calcium movement to cause contraction (because they arent in the sarcoplasmic reticulum)
T-tubule L-type Ca2+ channels open what other channels?
They physically open the sarcoplasmic-reticulum-ryanodine-Ca2+ channels - this calcium influx is sufficient to induce contraction
Troponin I
`
Physically in the way covering the myosin-binding site on actin
Troponin T (TnT)
Pushes tropomyosin aside
There is optimal overlap between the actin and myosin filaments
A single contraction of skeletal muscle is most likely to be terminated by?
Removal of sarcoplasmic Ca2+
Why does rigor mortis set in?
Decreased ATP levels
The diagram illustrates the isometric length-tension relationship in a representative intact skeletal muscle. Use the letters in the diagram to identify the contribution of non-contractile muscle elements to total tension.
C
Tetanic contraction of a skeletal muscle fiber results from a cumulative increase in the intracellular of?
Ca2+
Which of the following situations is most likely to increase the proportion of Type I fibers in skeletal muscle?
Aging
Primary source of ATP in type 1 and type 2B fibers
Type I - oxidative phosphorylation
Type 2 - glycolysis
Myoglobin content in type 1 vs. type 2B fibers
Type 1 - high
Type 2B - low
Duchenne’s muscular dystrophy we see a decrease in what fibers first?
Fast twitch, specifically type IIX
What type of muscle fiber increases with type II diabetes?
The fast twitch muscle fibers increase with type II diabetes
Mini end-plate potentials
Are single vesicles that are released and produce a small 0.4 mV voltage deflection
These are calcium independent processes - why mini end-plate potentials are normal in Lambert-Eaton syndrome (impaired presynaptic volateg-senesitive Ca channels)
What is the “sensor” for smooth muscle
Calmodulin
What inhibits the contraction in smooth muscle
Phosphatase
Multi-unit smooth muscle
Electrical isolation of smooth muscle cells allows for finer motor control
Iris and ciliary body of eye
Piloerector muscle
Larger blood vessels
Smaller airways
Unitary (visceral) smooth muscle
Gap junctions permit coordinated contraction
Gut
Uterus
Arterioles
Bladder
Action potential of smooth muscle
Comparison to other muscle
Phasic vs. Tonic contraction of smooth muscle
Calcium interacts with troponin on the _________ , in skeletal muscle
Calcium interacts with troponin on the thin filaments in skeletal muscle
In smooth muscle, calcium binds to _______ , activates ______ ______ _____ ______ , which then activates (by phosphorylation) __________
In smooth muscle, calcium binds to calmodulin, activates a myosin light chain kinase (MLCK), which then activates (by phosphorylation) myosin light chains.
Calcium activates ______ in skeletal muscle, while it activates ______ in smooth muscle
Calcium activates thin filaments in skeletal muscle, while it activates thick filaments in smooth muscle.
Excitation contraction coupling in smooth muscle
The calcium signal diagram
Excitation contraction coupling in smooth muscle
List the different types
Electrical coupling - voltage gated Ca2+ channels open when the cell is depolarized - can be action potential or subthreshold depolarization
Pharmaco- (mechanical) coupling:
1. Cell membrane ligand gated Ca2+ channels
2. Ligand generation of IP3 which initiates Ca2+ release from SR
Both mechanisms may operate at the same time (norepi and serotonin can activate both pathways in the same cell)
Biochemical agents that stimulate contraction of smooth muscle
ACh
NE
Angiotensin II
Smooth muscle that exhibits rhythmical contraction in the absence of external stimuli also necessarily exhibits which of the following?
A. Intrinsic pacemaker wave activity
B. Higher resting cytosolic Ca2+ concentration
C. Hyperpolarized memebrane potential
D. Action potentials with “plateaus”
Intrinsic pacemaker wave activity
Generally seen in GI smooth muscle
The sensitivity of the smooth muscle contractile apparatus to calcium can be altered by calcium-independent mechanisms. An increase in calcium sensitivity can be attributed to a decrease in the levels of which of the following substances?
Myosin light chain phosphatase (MLCP) activity
The delayed onset and prolonged duration of smooth muscle contraction, as well as the greater sustained force generated by smooth muscle compared with skeletal muscle, are all consequences of which of the following?
Slower cycling rate of the smooth muscle myosin cross-bridges
Which of the following best describes an attribute of visceral smooth muscle not shared by skeletal muscle?
Contractions in response to stretch
Smooth muscle contractions are highly resistant to fatigue because:
Slow cross bridge cycling and dephosphorylation of myosin light chains in the latched state
Unitary and multi unit smooth muscle differ in this characteristic or property.
Unitary smooth muscle cells are connected by gap junctions but multiunit smooth muscle are not
Smooth muscle contraction is terminated by?
Dephosphorylation of myosin light chain
Which of the following best describes an attribute of visceral smooth muscle not shared by skeletal muscle?
Contractions in response to stretch
Stretching smooth muscles opens mechanically gated Ca2+ channels which induces contraction
During pregnancy, why does the uterus behave as a unitary smooth muscle?
Estrogen promotes gap junction formation between smooth muscle cells
Nitric oxide MOA
Diagram
A drug that causes muscle tightness is likely inhibiting which of the following transporters?
A. Voltage-gated sodium channels
B. Sarcoplasmic ER ATPase (SERCA)
C. Ryanodine receptor calcium channel
D. Dihydropyridine receptor, L-type calcium channel
E. Nicotonic acetylcholine receptor
B. Sarcoplasmic reticulum endoplasmic reticulum ATPase (SERCA)
A defect in which of the following proteins produces malignant hyperthermia?
A. AChR
B. Mysoin light chains
C. SERCA
D. Ryanodine receptor calcium channel
E. L-type (dihydropyrodine receptor) calcium channel
D. Ryanodine receptor calcium channel
Ion flux through what channel is associated with the upstrok of action potentials and contraction in smooth muscle?
Voltage-gated calcium channels
Ragged red fiber
Due to defective oxidcative phosphorylation
Occurs in Pt’s w/ myoclonic epilepsy w/ ragged red fiber (MERRF) due to point mutations in mitochondrial DNA that result in dysfunction of proteins in the ETC
Has variable expression within families due to heteroplasmy (heterogeneity of mDNA within a cell - caused by selective distribution of mitchondria w/ mutated DNA)
MERRF causes myoclonus, ataxia, weakness, and generalized epilepsy
Muscle fivbers w/ red inclusions that disrupt the normal fiber contour
An investigator is studying muscle contraction in tissue obtained from the thigh muscle of an experimental animal. After injection of radiolabeled ATP, the tissue is stimulated with electrical impulses. Radioassay of these muscle cells is most likely to show greatest activity in which of the following structures?
AMBOSS
The outer segments of the A band are the sites where actin and myosin filaments overlap and form cross-bridges via the myosin heads, which bind and hydrolyze ATP. Following injection of radiolabeled ATP, radioassay is most likely to show the greatest activity in the A band of the sarcomere.
AMBOSS
