L5: Physiology of Muscle Contraction Flashcards
how does troponin work
1) 4 calcium ions bind to troponin C
2) in heart TnC only binds to 3 Ca2+
3) causes troponin to change its conformation
4) Conformational changes in troponin shut off TNI
5) Tropomyosin-troponin leaves F-actin groove and unmasks the myosin binding site on actin
6) Next myosin heads make cross bridges cycling to actin
7) myosin breaks down Atp
8) myosin pulls thin filaments
what does the significance of the total TNI marker
Total TnI = marker for total muscle breakdown
what does the cardiac TNI signify
Cardiac TnI = marker for myocardial infarct
describe cross bridge cycling
contraction depends on the binding of myosin heads to thin filaments at specific sites
-In resting state of sarcomere, myosin heads are blocked from binding to actin by tropomyosin
this occupies the specific binding sites -( in F-actin double helical groovwe)
describe the relationship between force generation and sarcomere length (study slide 7)
-Increase in overlap of thick and thin filaments provide an increase in force
core memorisation of cross bridge cycling
1) myosin releases actin
2) myosin head cleaves ATP
3) Myosin head binds actin
4) power stroke performed
what occurs in rigor mortis
- Atp depleted after death
- muscle cell does not requester ca2+ into SR, so increase in cytosolic ca2+
- Ca2+ allows cross bridge cycle contraction until ATP and creatine P runs out
- w/O ATP- myosin stops just after power stroke, so actin still bound to myosin, and this ends when muscle tissue degrades in 3 days
Info on creatine
1- creatine found in muscle fibres
2- Phosphorylated to creatine phosphate
3- this is how energy is stored in the muscle
what occurs to creatine phosphate during cross cycling
When cross bridge cycling hydrolyses ATP to ADP + pi, creatine phosphate donates a high energy phosphate to ADP restoring it to ATP
ATP levels must be kept stable - buffering and regeneration
the reaction is catalysed both ways by creatine phosphokinase
difference between creatine and creatinine
Creatine is a small molecule that can accept high energy phosphate bonds from ATP
- creatine-phosphate is the above molecule after phosphate has been added to it
-creatinine is a diagnostic marker for kidney function
and is the breakdown product of creatine
what is CPK a biomarker for
Muscle destruction
detected by antibodies
describe the calcium gradients
there are 2 calcium gradients;
- extracellular vs cytosolic free calcium
- SR vs cytosolic free calcium
It is the efflux of calcium from the SR to the cytoplasm that provides most of the calcium
the depolarisation of muscle
1- ACh leads to muscle depolarisation
2- active nicotinic AChR leads to net inward current
3- depolarisation spread via T-tubules
4- local action potentials trigger calcium efflux from terminal cisternae across membrane of sarcoplasmic reticulum into fibre cytoplasm
describe E-C coupling
Ryanodine receptor (RyR)
in SR membrane releases ca2+ from SR triggered by voltage sensor on ca2+ channel
SERCA in SR membrane pumps ca2+ back into SR and requires ATP
what is the molecular basis of tetany
- single AP leads to calcium release from SR which leads to twitch
- Ca2+ ions are rapidly pumped back into SR leading to the end of twitch
- Frequent Aps lead to insufficient calcium resequestration and summation of contraction