Muscle Facts Flashcards
Arrangement of Sarcoplasmic Reticulum in skeletal muscle
Dense network of tubules outside of each myofibril, forming terminal cisternae on either side of T-tubules
Describe excitation-contraction coupling in striated muscle
Via CICR: Calcium-Induced Calcium Release
- AP travels down T-tubule
- Dihydropyridine receptors (sarcolemma) open
- Ca++ influx
- Ryanodin receptors (SR) open
- Ca++ released from sequestrin right beside receptors
- muscle contraction
- NCX (Na+/Ca++ eXchanger) pumps Ca++ back through the sarcoplasm
- SERCA pumps CA++ back into SR
Role of motor end plate
Start AP across myofiber to T-tubules
Describe myotendinous junction (skeletal muscles)
Arrows (projections) of myofibers insert into connective tissue
What does the dystroglycan-containing complex bind?
F-actin inside the cell, basal lamina outside (through the sarcolemma)
Organization of skeletal muscles: connective tissue
Epimysium -> Perimysium -> Endomysium (decreasing density)
Describe how increasing [Ca++] leads to muscle contraction (in presence of ATP) in skeletal muscle
- Ca++ binds troponin
- Moves tropomyosin away from myosin-binding sites on actin
- Myosin (bound to ADP & Pi) binds actin (forming cross-bridge)
- Power stroke drags actin towards M-line of sarcomere, releasing ADP & Pi
- Myosin head binds ATP, releasing actin (removing cross-bridge)
- ATP hydrolysis cocks myosin head
- Repeat (from binding actin) until Ca++ removed & tropomyosin again covers myosin-binding sites
Role of dystroglycan-containing complex (skeletal muscles)
Allow cross-talk between the inside and outside of the myofiber (cell)
Motor neuron arrangement in skeletal muscle
Cell body in ventral horn of spinal cord; branches to have one axon terminal per myofiber in the motor unit
Two molecules needed for skeletal muscle contraction
Ca++, ATP
Arrangement of myofibrils in myofiber (skeletal muscle)
Parallel, separated by sarcoplasmic reticulum and mitochondria
Role of Sarcoplasmic Reticulum (all myocytes)
Store & release Ca++
Skeletal muscle function
Locomotion
Posture
Respiration (diaphragm & intercostal muscles)
Organization of skeletal muscles: muscle tissue
Muscle -> Fascicle -> Muscle fibers -> Myofibril (-> Myofilament *not “wrapped”)
Status of nucleus in skeletal muscles
Multi-nucleated; nuclei at periphery (just under membrane)
Location of sarcoplasmic reticulum & mitochondria in myofibers
Between myofibrils
Function of cardiac muscle
Heart beat
Symptoms of muscular dystrophy
- Muscle wasting & degeneration
- Mental retardation
- Waddling tip-toe walk
- Spinal curvature
- Calf muscle pseudohypertrophy
- Frequent falls, and inability to get up without use of arms
- Poor fine motor skills
- Weak diaphragm (trouble breathing -> lack ability to clear out pathogens -> may lead to death by pneumonia)
Effect of muscle stimulation with break in between
Muscle relaxes fully in between, resulting in two separate, same-size twitches
Cause of Becker Muscular Dystrophy
Mutation in dystrophin gene results in shortened (semi-functional) dystrophin protein
Result of two stimuli with partial muscle relaxation in between
Summation: second twitch is larger
Profile of dystrophin protein
N-terminus … actin-binding domain … rod-like domains w/4 hinge (Pro-rich) domains … Cys-rich domain (binds dystroglycan-containing complex) … C-terminus
Effect of botox
Botulism: prevents ACh release -> paralysis
Location of dystrophin gene
Short arm of X-chromosome; linked to muscular dystrophy
Result of prolonged, closely-spaced stimulation of muscle fibers
Tetanus: sustained maximal contraction because no relaxation between stimuli
Cause of Duchenne Muscular Dystrophy
Mutation in dystrophin gene results in early stop codon -> shortened dystrophin protein missing Cys-rich domain is target for protein degradation (complete loss of function)
Treatments for Muscular Dystrophy
Myoblast/stem cell transplant
Pharmacological treatment
Deliver DNA for microdystrophin (DMD only)
Exon skipping (DMD only)
Describe exon skipping treatment for DMD & drawbacks
Use antisense oligonucleotide to cover the exon containing the early stop codon plus enough other codons to restore reading frame
Results in BMD (less severe than DMD)
Doesn’t work if stop codon is in a critical domain (e.g. Cys-rich or actin-binding domain)
Result of Duchenne Muscular Dystrophy
Sarcomeres become unaligned, killing the myofiber
Describe myoblast/stem cell transplant treatment for MD & drawbacks
Inject myoblasts or stem cells to replace lost myofibers
Difficult to inject large cells
Result of muscular dystrophy
Holes produced in sarcolemma from force
Usually make new myocytes, but run out of ability
Holes filled with connective & adipose tissue
Describe the pharmacological treatment for MD
Inject compound to increase utriphin expression (80% similar to dystrophin) to compensate
Describe DNA delivery treatment for MD
Insert DNA for microdystrophin (short protein containing only components of dystrophin essential for semi-functional protein)
Function of dystrophin/dystroglycan-containing complex
Force dissipation into basal lamina to prevent muscular degeneration over time
Describe filament mechanism of contraction in smooth muscle
- Contractile units (lateral) shorten
- Pulls dense bodies and dense plaques closer together
- Pulls “mesh” of thin filaments tighter around cell
Compare response time of smooth and striated muscle, between signal and contraction
Slower in smooth muscle, typically
Describe (autonomic) innervation and AP propagation in multi-unit smooth muscle
- Abundant innervation by several autonomic innervation
- Separated into independent contractile units
- Few gap junctions
Describe cardiac muscle fibers
Short, branched, attached at ends to other myofibers by intercalated disks; sarcomere arrangement similar to skeletal muscles
Organization of smooth muscle around arteries and veins
Forms tunica media (middle layer); thicker in arteries to sustain higher pressures
Location of multi-unit smooth muscle
- hair follicles
- large blood vessels
- small airways in lungs
- iris & lens of eye
Form of intercalated disks
step-like: transverse and lateral components
Organization of smooth muscle around intestines
Longitudinal & circular layers (coordinate for peristalsis; allow forwards movement only)
Function of smooth muscle
Constriction of viscera and blood vessels
Location of mitochondria and neurotransmitter vesicles in motor neurons for skeletal muscle
Axon terminal buttons
What does smooth muscle have instead of T-tubules?
Caveolae (goblet-shaped)
Describe (autonomic) innervation and AP propagation in single-unit smooth muscle
- Less abundantly innervated by autonomic neurons than multi-unit
- Many gap junctions - spread AP throughout
- Single contractile unit (many myocytes contract together)
Describe nuclear state of smooth muscle cells
1 central nucleus per myofiber, takes on corkscrew shape during contraction
Organization of smooth muscle around stomach
Longitudinal, circular and oblique layers (allow food to be mixed in multiple directions)
Describe pharmacomechanical coupling in smooth muscle fibers
- NO CHANGE IN V_m*
- Hormone/neurotransmitter binds membrane receptor
- Increase cytoplasmic [IP3] (inositol triphosphate)
- Bind IP3 receptors on peripheral SR face
- Opens ligand-gated Ca++ channels
- Usual mode of contraction via myosin & actin
Component(s) of transverse region of intercalated disks (cardiomyocytes)
- zonula adherens (attaches f-actin of terminal sarcomeres to plasma membrane)
- desmosomes (keep adjacent fibers together during contraction)
Organization of caveolae in smooth muscle fibers
Rows, alternating with rows of dense plaques
Fact: Smooth muscle cells have no T-tubules
(fact)
Component(s) of lateral region of intercalated disks (cardiomyocytes)
Gap junctions (allow free ion movement between cells for faster AP transmission)
Describe general autonomic innervation of smooth muscle
- Post-ganglionic nerve branches in muscle
- Varicosities slightly removed from muscle
- NT diffuses through the space
Describe excitation-contraction coupling in smooth muscle
- V-gated channels open: extracellular Ca++ into sarcoplasm
- Ryanodin receptor releases Ca++ from SR (CICR)
- Ca++ binds CALMODULIN
- Ca++/Calmodulin binds MLCK
- phosphorylates 2 myosin light chains
- allows usual myosin contraction
Location of mitochondria and neurotransmitter vesicles in motor neurons for smooth muscle
Varicosities
Function of gap junctions in intercalated disks
Allow free ion movement between myofibers for faster AP transmission
Location of single-unit smooth muscle
- walls of viscera
- small blood vessels
Describe filament arrangement in smooth muscle
- Thin filaments arranged obliquely
- “Mesh” anchors sarcomere in cell
- Contractile units arranged laterally
- Filaments attached to dense bodies (cytoplasm) or dense plaques (plasma membrane)
Difference(s) between SR in cardiac and skeletal muscle
More sparse & contains less Ca++ in cardiac muscle; 1 cisterna per T-tubule
Location of SR in smooth muscle fibers
Below caveolae (for sensitivity to Ca++ influx through dihydropyridine receptors)
