Muscle Flashcards
Which of actin/myosin is thick and which is thin?
Actin = thin, myosin = thick
Which troponin subunit binds to Ca2+?
C subunit
What is the physical chain of events of the cross bridge cycle?
Detatch, attatch, rotate, unit force
What are the two states of myosin?
Ground or activated
What is maximum force called in a muscle?
Isometric
Which muscle type doesn’t have troponin?
Smooth
How is contraction initiated in smooth muscle?
Ca2+-regulated phosphorylation of myosin by MLCK
What does Ca2+ bind to in order to activate MLCK?
Calodulin
How do you form a latch bridge in smooth muscle?
Remove phosphate when the cross bridge is formed
How many Ca2+-binding subunits does troponin subunit C have? How many are high-affinity regulatory?
4,2
What causes the upstroke and downstroke of the early surface wave?
Upstroke = Na+ channel activation, downstroke = Na+ channel deactivation, K+ channel activation, Cl- channel stabilises
Where must muscle be stimulated to get a contraction? Why?
Z lines because this is where tubular system is
What do DHP channels do?
Modified Ca2+ channels which detect voltage change and change configuration so interact and open Ryanodine receptor
What do “junctional folds” do?
Have active zones which contain the transmitter
What is in the synaptic cleft?
Nucopolysaccharide “glue” and has extracellular material called the “basal lamina”
Which enzymes makes ACh?
Choline acetyltransferase
Where is ACh localised to?
Basal lamina
What does “I” and “A” band stand for?
Isotropic, anisotropic
What is the selectivity filter of the ACh receptor?
Hydrophilic amino acids pointing inwards, rejects anions but cations can pass through
What makes up myosin?
Two twisted meromyosin strands (heavy head with S1 and S2 part and light tail)
What activates ATPase which reacts with actin?
MLCK
What does the cardiac muscle syncytium mean for its Ca2+ store?
More limited Ca2+ store
What is the process of the cross link cycle?
My and act both positively charged, need -ve phosphate to allow them to bind, phosphate is then lost so two +ve charges cause conformational change, another ATP needed so phosphate binds again and act and my let go
Why does heart have an intrinsic pacemaker rate?
Prolonged plateau and longer time to reach upstroke
What does effect of Cl- depend on?
Vm
Why is there a plateau in act pot?
Rapid upstroke from Na+ channels opening, these inactivate but Ca2+ channels open so depolarization maintained at 0mV until repolarisation by K+ channel
Stages of plateaued act pot?
Early rapid depolarisation, initial rapid depolarisation, plateau, terminal repolarisation, electrical diastole
Why does cardiac muscle show prolonged refractory period and have “excitability gap”?
To prevent tetanus, only one act pot for every beat
What is the T wave?
Ventricular repolarisation
What does the Na+-Ca2+ exchange in cardiac muscle cause?
Depolarisation
What is Ca2+ released by?
Phosphoinositide lipid
What is conduction like in the atria?
Poorly developed T system, wave of induced Ca2+ release, caveolae (membrane invaginations)
What does the funny current do?
The pacemaker current
What happens in the vagus nerve to the heart/what neurotransmitters are there?
Ach released in SA node, ACh and muscarinic K+ channel causes hyperpolarisation, needs longer funny current so HR down
What happens in the accelerator nerve to the heart/what neurotransmitters are there?
Sympathetic to all over the heart, NA and A from adrenal medulla increase rate of pacemaker depolarisation, enhanced Ca2+ channel activation, increased cAMP, more Ca2+ so higher heart rate, act pot shortened
Where is the AV node?
On the right where blood comes in
What causes the funny currents?
HCN channels in membrane open below threshold potential
What happens to DHP/RyR in cardiac muscle?
Aren’t linked, DHP is now a calcium channel which changes conformation, Ca2+ enters cell and binds to RyR allowing more Ca2+ release (Ca2+-induced Ca2+ release) so more contraction
How does cAMP affect HCN?
Increases leak to increase heart rate
How does ACh affect cAMP?
Decreases cAMP so decreases HCN leak so heart rate slows
Why does Ca2+ contribute to the action potential in cardiac muscle?
Because it crosses the membrane
Why does myotonia congenita occur?
Cl- channels have defect causing sustained muscle tension
Why isn’t much K+ required for a high concentration in the T tubules? Which channels make sure the cell still goes negative?
The T tubules are small, Cl-
What is a MEPP?
Miniature end plate potential, random release of vesicles from Ca2+ leaking
What are the subunits in nicAChR?
5 subunit, 2 where ACh binds (alpha) then beta gamma and delta.
What is a motor unit?
All muscle fibres innervated by one nerve
What influences the frequency of MEPPs?
[Ca2+], [Mg2+], [K+], osmotic pressure
What are the steps to test the NaKATPase?
Inject radio-labelled ATP, will drop as there’s less in cell so harder to pump out, remove all K+ ions so drops but can still use Na+ to stay working, check it’s not broken, add DNP and it slows, wash away and check again
How do you test the electrogenic effect of the NaKATPase?
Rubbing skin causes lot of act pots and membrane potential drops (pup overactive and Na+ in continuously), if you hyperpolarise it too much you can’t reach the threshold pot
How do you get malignant hyperthermia?
Anaesthetic gas and RyR
Which muscle’s method of contration doesn’t affect the act pot?
Skeletal
When are inwardly rectifying channels open?
When cell is negative
Which stroke is which is pacemaker potentials?
Na Ca K
How do hormones affect calmodulin?
Hormone to PLC to PLC to calmodulin
Which enzyme forms the latch bridge?
Myosin phosphatase
Where do you find MSP
At end of capillaries
What is the ANREP effect?
Heart contracts harder and ejects more so end systolic volume is reduced instead of being the same each time
Which receptors in parasympathetic?
NicAChR then muscAChR
Which receptors in sympathetic?
nicAChR then NA
Why do you get larger force for same Ca2+ release with NA?
Only two Ca2+ needed
Which muscle type has no sarcomeres?
Smooth
What is the anchor in smooth muscle?
alpha-actinin
What is the control of the crossbridge cycle called in smooth muscle?
Covalent regulation
What phosphorylates caldesmon? What activates this?
PKC activated by DAG
What is a second messenger which open Ca2+ channel in the SR in smooth muscle
IP3 from PIP2 (made when receptors activate PLC)
What is the secondary activate transport in cardiac muscle?
Sodium calcium exchange (one Ca out, three Na in)
Which muscle type has dyad rather than triad junctions?
Cardiac
What does inward rectification do?
Increases membrane resisitance and reduces calcium flow that’s generating the plateau so minimises Ca2+ gradient dissipation, minimises leak currents and therefore reduces the amount of inward current reuqired to sustain the plateau phase of the cardiac muscle action potential
How many binding sites does troponin have in cardiac muscle?
Three not four
How is contraction strength regulated in cardiac muscle?
Amount of Ca2+ because one excitation stimulates all muscle cells
What stabilises the AChR pentamer?
Lipophilic side chains point outwards towards the hydrophobic interior of the lipid bilayer
Why is the EPSP slower than the EPSC?
Because of the time necessary to charge and discharge the muscle membrane capacitance
What happens to the EPSC as Vm gets larger and larger?
First gets smaller, then disappears, then gets larger in the opposite outward direction
What is the reversal potential of the EPSC?
0 mV
Why do EPSCs speed up with depolarisation?
Some voltage-dependence of the ACh gating (energy efficient because the conductance switches off faster when it’s no longer needed for depolarisation)
What is the active ingredient of curare?
D-tubocurarine
How does curare work?
Competes with ACh for binding on post-synaptic receptor but can’t cause channel opening
What does eserine/physostigmine do?
Blocks acetylcholinesterase in the synaptic cleft so can measure how much ACh is released
What does alpha-bungarotoxin do?
Binds tightly to and blocks AChR so if you radioactively label it you can count the AChRs
What does alpha-latrotoxin do?
Massive release of pre-synaptic transmitter causing neuromuscular block by ACh depletion
What does botulinum toxin do?
Prevents ACh release
What changes MEPP frequency?
Decreased by decreased internal calcium or increasing magnesium, increasing by increasing external K+ or osmotic pressure
What is a consequence of the cable properties of muscle?
Without regenerative, inward current through voltage gated Na channels, the depolarisation fades with distance and more and more of the endplate current leaks away
Abnormalities in which protein have been associated with the pathogenesis of muscle dystrophy?
Dystrophin
What are the light and heavy strands of myosin made from?
Meromyosin
Where is the ATPase activity in the myosin head?
The S1 fraction
What is the structure of tropomyosin?
Rod shaped, forms alpha helical subunits which get packed into the groove formed by intertwisted helical actin chains
What are the three troponin subunits?
TnC, TnT and TnI
Where does tropomyosin go during activation?
Deeper into the actin groove
Which part of myosin is flexible?
Link between S1 and S2 segments
How many twitches is there enough ATP for in the cell?
8
How many twitches is there enough phosphocreatine for?
100
How many of the TnC binding sites have high Ca2+ affinity?
Two out of four
How much of the total tubular surface area do triads make up?
70%
Why do resting skeletal muscle cells show chloride conductance?
Stabilises membrane potential between electrical activity episodes
Why do you get myotonia congenita?
Deficiency/absence of functioning chloride channels causing repetetive action potential firing
What results from conformational changes of voltage sensor?
Small currents or charge movements
In skeletal muscle what does the elevated cytosolic calcium represent?
Release from SR stores (none from extracellular space)
What triggers malignant hyperthermia?
Halothane (RyR defect)
What moves calcium back to the SR?
Ca-ATPase (two calcium per one ATP)
What is calsequestrin binding ratio for calcium?
1:45
What are the five phases of the ventricular action potential?
Very rapid depolarisation, initial brief rapid repolarisation, plateau, terminal repolarisation, electrical diastole
How often do the SA node pacemaker cell discharge?
60-80 times/min
How often do the AV node cells discharge?
40-60 times/min
How often do the Purkinje cells discharge?
30-40 times/min
What takes over if there is severe SA node inhibition?
AV node or Purkinje fibres
WHat is different in conducting tissues of the heart?
Fewer myofilaments, faster impulse generation and propogation, can function as pacemakers
WHy does SA node determine overall HR?
Highest automaticity
WHat are the two His bundle fans called?
Right (smaller) and left
What is the left His bundle divided into?
Anterior and posterior
Why is smooth muscle spiking activity not prevented by tetrodotoxin?
Produced by voltage gates Ca2+ channels
What restores cytosolic calcium levels in cardiac muscles?
Ca-ATPase pumps, Na-Ca exchange (uses Na gradient energy)
How does digitalis and other cardiac glycosides work?
Block sodium pump and allow increase in intracellular sodium concentration
What is the Bowditch effect?
Myocardial contractility increases with heart rate
