Muscle biochemistry Flashcards
5 functions of muscle
- locomotion
- autonomic response - dilation
- homeostatis - BP, temp
- thermal generation
- metabolic regulation
2 things that create strength in mucles
- four fascia
2. many small compartments
descending order of muscle
body>fascicle>fiber>fibril>filament
4 ways muscles maintain coordination
- nerve transmission
- multinucleated cells
- SR
- T-tubules
define z-line
alpha actinin - where actin attaches
define z-line to z-line
sarcomere
define A-band
where think filaments exist
define H-band
space between myosin and actin - zone of functional reserve - that filaments can move against each other
define I-band
distance between mysoin and z-line - also zone of functional reserve
4 basic components to thin filament
- G-actin - monomers
- F-actin - double helix of g-actin
- tropomyosin - string that associated with actin
- troponin - complex of Ca regulated contraction
3 types of troponin and what they bind
- T- binds tropomyosin
- I - binds f-actin
- C - binds Ca
what happens to troponins in MI
releases
3 requirements of WHO def of MI
- EKG changes
- elevated cardiac enzymes
- typical physical symptoms
how many Ca can a trop. C bind?
4, but usually has 2 bound already
what happens when trop C binds Ca?
conformation change>allows myosin to bind actin>contraction
what is required for myosin to move forward to bind actin?
ATP
why is dose response of drug not linear
cooperativity of binding of Ca
first step in contraction
release ACh
what does ACh receptor release
small volume of Ca into T-tubule
what allows Ca into sarcolemma
L-type channel
what does Ca stimulate inside fiber
ryanodine receptor on SR
what does ryanodine receptor do?
releases large amount of Ca from SR
what does Ca do inside fiber
enters filament and bind to troponin
3 small ways to remove some Ca from fiber
- pump out for cost of ATP
- Na/Ca pump, then need to pump out Na/K pump for cost of ATP
- mitochondria can absorb some
biggest way to get Ca back into SR
SERCA2a - ATP dependent
what is major inhibitor of SERCA
phospholambin (PLB) - prevents quick contractions
how to inhibit PLB
phosphorylate via PKA - allows contraction
what can be given to stimulate PKA
epinephrine via cAMP
what happens if L-type channel is dysregulated
arrythmias
what happens if mitochondria absorbs too much Ca
apoptosis
what happens if no reuptake
can’t release any > no contraction
2 drugs that increase heart contraction
- milronone - inhibits phosphodiesterase>so doesn’t break down cAMP>more PKA>PLB is phosphyslated>allows SERCA to pump
- dobutamine - via Beta-1 andronergic receptor>activates adenylate cyclase>more cAMP
what do catecholamines (epinephrin) do
also stims Beta-1 receptors, less specific and lead to blood vessel dilation, which can drop BP
what is malignant hyperthermia
mutation of ryanadine receptor that make it super reactive>pumps out Ca like crazy and overwhelms ATP use in SERCA > muscle breakdown and acidosis
5 things that happen in hyperthermia
- cells contract but don’t release
- ATP hydrolysis - overheat
- lose membrane potential - myoglobin in kidney
- leads to apoptosis
- releases H into blood - acidosis
2 types of muscle relaxants, what and how they work
- depolarizing - succinylcholine - bind to Ach receptor when open - get inital contraction and then can’t bind again
- non-depolarizing - vecuronium - bind to closed receptor and don’t allow reactivation
how to reverse muscle relaxants
neostigmine - stimulates release of Ach to outcompete neuromuscular blockade
L channel diffs. between cardiac and skeletal muscle
cardiac - L-channel v. important and triggers RYR, t-tubules better developed
communication diffs. between cardiac and skeletal muscle
cardiac - electrochemical
skeletal- multinulear
t-tubule diffs. between cardiac and skeletal muscle
cardiac - large
skeletal- small
receptor diffs. between cardiac and skeletal muscle
cardiac - many hormones
skeletal- Ach
cross bridge cycling diffs. between cardiac and skeletal muscle
cardiac - rapid strong contractions
skeletal- slower consistent contractiosn that don’t tire
need for ECF Ca diffs. between cardiac and skeletal muscle
cardiac - Ca essential
skeletal- Ca not essential
**what is frank-starling law comparison of
stroke volume vs. ventricular end-diastolic volume
2 things that increase stroke volume
- muscle contraction
2. cardiac output
what determines ventricular diastolic volume
functional reserve of sarcomere
3 ways of increasing contractility
- sympathetic stimulation (epinephrine)
- inotrpoes - milrinone or dopamine
- luisotropes - relaxes heart of over stimed
protein missing in smooth muscle
troponin
what does Ca bind to in smooth muscle
calmodulin
what does calmodulin do?
upregulates MLCK > phosphrylates MLC > contract
what does cAMP do in smooth muscle
inhibits MLCK > no contractions
what controls smooth muscles (2)
- autonomic system
2. hormones
how does B-andronergic control of smooth muscle happen
epinephrine>Beta2 receptor>incr. cAMP>activates PKA>phosphorylates MLCK which inhibits its action>relaxation
how is NO released
pressure or bradykinins (inflammation) in endothelial cell produce NO
how does NO dilate smooth muscle
NO moves into muscle cell and increases cAMP> inhibits contractions
3 ways to treat pathologic lung vasoconstriction
- direct vasodilation via inhaled NO
- increase smooth muscle cAMP : viagra
- block vasocontriction - bosetan - antagonist of endothelin receptor
how to change blood flow up and down
dilate: nitroglyrcerine or nitrates
contract: beta-1 andrenergic blockers
What happens in myasthenia gravis
antibodies to ACh receptors - chews them up>no contraction
treatment of myasthenia gravis
incr ACh at NMJ - remove thymus or give pyridostigmine
what causes lambert eaton syndrome
anitbodies against presynaptic voltage-gated Ca channels
what does botulism toxin do?
prevetns Ach release by digesting SNARE, a protein responsible for exocytosis
6 possible causes of loss of muscle stim.
- upper motor neuron damage
- lower motor neuron damage
- congential metabolic disease
- chonic illness - atrophy
- immune reactions
- autoimmune disease
what happens in muscular dystrophy
loss of anchor protein means muscle can’t pull agains anything when it contracts
muscle energy source at rest
lipids
muscle energy source in low excercise
glucose and glycogen
muscle E source in high excrecise (2)
- anaerobic glycolysis
2. creatine phosphate conversion to ATP
