Flashcards
Cardiac Muscle
Cards in this deck (116)
- 1where does cardiac muscle originate from during development?neural crest
mesodermal cells form cardiac progenitor in the neural crest - 2why do we need a circulatory system?diffusion is too slow
- 3what do cardiac progenitor cells go on to form?fibroblasts to cardiac muscle cell
- 4what are some of the roles of fibroblasts?1) synthesises the extracellular matrix and collagen
2) structural framework for animal tissues --> also plays critical role in wound healing
3) common cell of connective tissue - 5what does the 'blast' part of fibroblast denote?--> stem cell or a cell in an activated state of metabolism
- 6why are fibroblasts said to be morphologically heterogenous?diverse appearances depending on their location and activity
- 7—cell type origin
- 8how do we produce a prototypic cardiac cell?we can now take a fibroblast from skin and convert it into PCC
enables us to examine the drugs that could be used
DO THIS BY CONTROLLING TRANSCRIPTION FACTORS - 930-60% cells are fibroblasts but only 2% wight, true or false?true
- 10describe the cellular structure of the heartlots of collagen and elastin associated with fibroblasts
muscle cells arranged in fibrils
intercalated disks between fibres allow them to be electrically coupled (gap junctions)
- 11what is the myocardium?the muscle tissue of the heart
striated muscle (sarcomeres) with 1-4 nuclei (usually only one) - 12once killed (post-infarction), can you grow new cardiac muscle cells?no
- 13what do we mean when we say the heart is an 'electrical syncytium'?all cells in heart become electrically excited when one does
- 14what structures are put into place to allow the heart to be an electrical syncytium?intercalated disks contain gap junction proteins --> allows electrical current to flow from cell--> cell
- 15what does the heart remodel in response to? how does it do this?in response to disease
supportive network can change the frame shape often shortening the cardiac muscle fibres - 16what can cardiac myocytes provide in the heart?shortening
- 17how does the heart achieve a spherical contraction?cardiac muscle fibres twist around the walls of the heart - due to the different orientation of the fibres, when they contract the heart twists --> squeezing the chambers and decreasing their volume
get a 3-D contraction from a 1-D linear cellular contraction by organising the tissue in 3 dimensions --> change in fibre direction
change 180 degrees - 18cardiac fibres twist around the heart diagram
- 19how can people (for a limited time) survive a heart puncture without medical intervention?twisting contraction temporarily plugs hole
- 20why is the cardiac muscle described as myogenic? what does this mean?acts as its own electrical pacemaker --> electrical activity starts within the heart (self-generated)
- 21difference between left and right side of heart?right --> lungs
left --> body (thicker and more powerful - generate higher pressure) - 22each cardiac cell has roughly how many sarcomeres?50
- 23what type of metabolism do cardiac cells have?oxidative metabolism
require a continuous oxygen supply to continue normal function - 24how much does the volume of the heart change when it contracts? what doesn't change? how is the blood ejected from the heart?1) volume of ventricles changes by about 50%
2) outside of heart hardly seems to move
3) fibres twisting around causes wall thickening and changes the volume of the ventricles and causes ejection of blood
all seen by cMRI - 25what is a sarcomere?contractile machinery that is organised into a banded structure
- 26what are myocytes?long, tubular cells that develop from myoblasts to form cardiac muscle in a process called MYOGENESIS
- 27what is the first part of the cardiac activation sequence? what is the ion responsible?1) pacemaker signal
2) uptake stroke is quite slow as it is due to Ca2+ uptake and not Na+ - 28describe the route of the electrical signal through the heart1) starts at SA node
2) travels through atria
3) travels to AVN
4) travels through bundle of HIS (purkinje fibres) causing ventricles to contract from the bottom up - 29describe the waveform of the signal at AVN?similar to SAN
- 30compare the firing rate of the AVN to the SAN - what does this mean?firing rate of the SAN is faster than the AVN--> AVN never usually gets to fire its own AP
- 31what happens in sick sinus syndrome?SAN doesn't work - AVN takes over
- 32how quickly does an AP travel through the AVN? why is this important?AP velocity through AVN is slow - gives atria a chance to finish contracting and top up ventricles before they start contracting
- 33explain the difference between an AP through the atria and the ventriclesabout the same size but longer lasting in the ventricles
- 34what does an ECG record?sum of action potentials throughout the heart
- 35what is the P wave?atrial contraction
- 36what is the QRS complex?depolarisation of the ventricular muscle
- 37what is the T wave?the difference in timing of depolarisation of the epicardium (outside tissue) and endocardium (inside tissue)
- 38what is each cardiac cell associated with?its own capillary
- 39how many nuclei do atrial cells have? ventricular?1) one
2) 2-3 - 40—
- 41what is the function of the sarcoplasmic reticulum?regulates Ca2+ concentration in cytoplasm of striated muscle --> Ca2+ store
gives 60-90% of the calcium needed - 42what are t-tubules?invaginations of the sarcolemma
allows depolarisation of the membrane to quickly penetrate to the interior of the cell
--> which shifts tropomyosin and allows myosin ATPase to bind to actin - 43what type of channel are t-tubules rich in?L-type Ca2+ channels
- 44what type of current is seen at the surface of the membrane of cardiac cells? what mediates it?calcium current mediated through L-type Ca2+ channels
- 45how does conductance from the surface membrane into the cardiac cell occur?at the junctional sarcoplasmic reticulum where the sarcoplasmic reticulum and the extended membrane meet the calcium induced calcium release gates
- 46what causes the red/brown colour of cardiac cells?MITOCHONDRIA
30% of cell volume - 47what % Ca2+ comes from inside the skeletal muscle? where does it come from in cardiac muscle?1) 100%
2) 90% from SR but significant amount comes from outside heart across sarcolemma - 48how is calcium released from the SR?RyR2 isoform (ryanonide receptor) on SR, open in response to Ca2+ --> calcium induced calcium release
- 49what is the structure of RyR2?made up of 4 identical subunits
one of the largest proteins in the body
have Ca2+ binding sites
located very near to L-type calcium channels - 50what determines the organisation of sarcomeres?ENVIRONMENTAL CUES
adhesion cues determine organisation
proteins are overturned every week so framework must remain constant - 51diagram of cardiac diad?
- 52what is a cardiac diad? what is it vital for?1) located at the sarcomere z-line, composed of a single t-tubule and the terminal cisterna of the sarcoplasmic reticulum
2) EXCITATION-COUPLING provides inlet of AP near to Ca2+ source allowing the wave of depolarisation to be coupled with wave calcium-coupled contraction - 53where are RyR located?near contractile machinery on SR
- 54what is a couplon?a functional grouping of RyR and DHPR (dihydropyridine receptors) with calcium release units
- 55what are the two proteins essential for excitation-contraction coupling1) dihydropyridine receptors (L-type Ca2+ channels) on external membrane
2) RyR which are the Ca2+ channels of the SR - 56with regard to L-type Ca2+ channels and RyR, does cardiac muscle have a more or less organised layout when compared to skeletal?less organised
- 57what do we mean by 'cardiac muscle works on ascending limb of length-tension curve'?increasing length increased force production
- 58how is Ca2+ the main regulator of contractility?increasing intracellular Ca2+ mobilisation (or influx) will INCREASE CONTRACTILITY
decreasing sensitivity to Ca2+ will decrease contractility - 59is the cardiac muscle contractile machinery is not normally fully activated?true
Ca2+ released not sufficient to maximally activate the muscles - 60which is the only ion that can trigger contraction?Ca2+
- 61what is aequorin?extracted from jellyfish
activated by Ca2+ and gives off blue light - 62what replaced aequorin?GFP
- 63what was shown in the Rudel and Taylor experiment? What was a disadvantage of this experiment?1) increased luminescence before contraction
2) high signal to noise ratio - 64—x
- 65where does the Ca2+ in the cell come from?70-90% is from the SR, the rest is carried from the external membrane by L-type Ca2+ currents
- 66what 2 things does cardiac contraction depend on?1) increasing length increases force production
2) amount of Ca2+ - 67how does sympathetic innervation affect contractility?1) increases the size of the Ca2+ store and increases release
2) gets heart to relax more quickly by decreasing sensitivity to Ca2+ - lusitropic effect, heart can beat more quickly increasing the net force - 68what are the 4 ways in which Ca2+ can be removed from the cell?1) ATP phospholamban (PLB) uptake pump in SR
2) NCX exchanger powered by ATP
3) uniport into mitochondria, activation and increase ATP production
4) activation of troponin activation of myosin - 69—x
- 70at what voltage does the L-type Ca2+ current switch on?-30mv
- 71what does DHPR stand for?dihydropyridine receptor
- 72what is the DHPR sensitive to?Ca2+
- 73what does the inward Ca2+ current carried by DHPRs contribute to?1) AP plateau --> long and prevents tetany
2) triggers E-C coupling
3) inhibited by SR release - 74at what voltage do DHPR channels open at? what is the normal resting potential?-40 mV
-80 mV - 75what substances stimulate DHPR?catecholamine
adrenaline/noradrenaline - 76what inhibits DHPRs? 3 things1) dihydropyridines (Ca2+ channel blockers)
2) magnesium
3) low plasma Ca2+ --> body usually keeps this constant as there are Ca2+ stores in the bone - 77what effect does caffeine addition have if introduced to the cell? what is this known as?1) there is increased activation of the sarcoplasmic reticulum, increased Ca2+ release INHIBITS L-type Ca2+ current
2) AUTOREGULATION - calcium inactivation of calcium current - 78what happens if the SR has high levels of Ca2+?inhibits entry of Ca2+ into cell so that NCX exchanger can remove Ca2+ from the cell
whatever Ca2+ comes in has to be removed by extrusion processes --> Ca2+ has to go back to where it came from - 79—as AP finishes, intracellular Ca2+ decreases and the Ca2+ current switches off
Na+-Ca2+ exchanger extrudes all the calcium that came in during that beat
- 80what do we mean by 'CICR doesn't cause regeneration'?doesn't induce more and more Ca2+ release
- 81when are DHPRs activated?during depolarisation - current flows during most of the plateau
- 82what contributes to maintenance of the current?NCX can bring Ca2+ into the cell helping to maintain the current
- 83what then happens with regard to the exchanger (NCX) during repolarisation?exchanger (NCX) moves into forward mode --> helping to remove Ca2+ from the cell
- 84what does depolarisation of the cell membrane suppress? why is this unusual?1) suppresses Ca2+ release
2) once Ca2+ influx has started, voltage should have no effect on RyR - 85what experiment showed that voltage had no effect on Ca2+ release?FLASH PHOTOLYSIS
- 86what did Stern explain?common pool models don't explain the behaviour (where all the Ca2+ flow in the same pool) -->
LOCAL CONTROL - 87what is local control?local [Ca2+] is key and not the whole cell concentration of calcium
- 88mouse vs rat Ca2+ fluxes
- 89what was discovered to confirm Stern's theory?calcium sparks
- 90what are calcium sparks?concentrated area of Ca2+ release --> doesn't propagate through cell
evoked by an AP - 91in 1993, how were the calcium sparks seen?confocal microscope with a Ca2+ indicator
in a resting cardiac cell there were brief flashes of Ca2+ in local regions - 92why do RyR see different amounts of Ca2+?RyRs are functionally distinct due to distance between them
a release of calcium from one RyrR doesn't simply propagate and activate the next RyR
this is because as soon as Ca2+ diffuses away, local [Ca2+] decreases - 93how far can the locally released Ca2+ travel?one sarcomere
- 94what does a doubling in fluorescence show?doubling in cytosolic [Ca2+]
- 95what is necessary for the cell to fill up with Ca2+?spatio-temporal summation when all the spark sites are synchronously activated
- 96what is one whole cell transient the summation of?all local currents
- 97—x
- 98ICa via DHPRs are served to trigger what?sarcoplasmic reticulum release
calcium current via DHPRs trigger local SR release in the form of calcium sparks - 99what are the two things that determines the Ca2+ transient amplitude?1) amplitude
2) and number (or frequency of firing) of calcium sparks that determine Ca2+ transient amplitude - 100how many Ca2+ sparks are responsible for the whole cell transient?10^4
- 101where are Ca2+ sparks seen? what do Ca2+ sparks resemble?cardiac, smooth and skeletal muscle
puffs due to IP3 receptor activation - 102what does the behaviour of local CICR explain?temporal release explains why terminating CICR - quantal events behave stochastically
if RyR hasnt fired before the current stops then it won't - 103what was the implications of Abbe's limit of diffraction?you can't see anything smaller than the wavelength of diffraction
- 104how can the resolution limit exceed the diffraction limit?exploit non-linear effects
- 105what is key during localisation microscopy?only one fluorophore active in each image at any one time so their diffraction patterns don't overlap
knowing we are seeing single molecules - 106what is the theoretical limit of resolution?250nm
- 107what is arbitrary precision?the molecule must be at the centre of diffraction --> can take away background/surrounding light
- 108what is the resolution of super resolution light microscopy? what is the alternative method?30nm
reversible photobleaching method - 109—DHPRs in the T-Tubules
- 110how are RyRs clustered?NOT CIRCULAR
clustered in around 25 RyRs - 111what is induction decay?disappearance of the inductive calcium release (CICR)
once CICR starts, SR begins to run out --> junctional depletion [Ca2+] decreases --> REGENERATION NO LONGER SUPPORTED
CICR DISAPPEARS
The RyR automatically switched off after a certain period of time --> induction decay - 112what increases rapidly with the square of local [Ca2+]?Probability of opening
- 113if the concentration of Ca2+ increased 100 fold, what does the Po of RyR increase by?10000
- 114system activates --> RyR produces Ca2+ in the diad --> amount of Ca2+ carried by RyR declines --> less and less likely RyR will stay opendue to geometry and stochastic gating
no inactivated state or sticky clustering - 115disease reduces colocalisation between what?DHPR and RyR in the disease state --> due to structural reorganisation
circle = calcium spark
- 116what isn't reduced in heart disease?protein expression
sarcomeres are still properly aligned - only the tubules aren't structured correctly
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- 2nd Year Developmental and Celluar Physiology of the Specialised Cell (Cell Signalling) Flashcards on Cardiac Muscle, created by William Chapman on 13/05/2016.
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