- ‘glue’ cells together - specialized adhesive protein complexes that localize to intercellular junctions and are responsible for maintaining the mechanical integrity of tissues

PBL 4 - control of cardiac contractility Flashcards by Olivia Swinn

what are the contractile/working cells of the heart?

cardiomyocytes

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what is the role of cardiomyocytes?

to contract in unison in order to provide effective pump action to ensure adequate blood perfusion of the organs and tissues

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what is the approx size of cardiomyocytes?

approx 100um x 20um — make up the bulk of the volume of the heart but constitute to only 30-40% of the total cell number

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how to cardiomyocytes attach to each other?

attach end-to-end via intercalated discs

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label this diagram of gap junctions

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what do gap junctions do?

transmit ionic currents from one cell to the next

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what is each gap junction made up of?

6 connexin subunits which form a hollow tube known as the connexon

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the connexon tube spans the 2-4nm intercellular gap, enabling the myocardium to what?

to act as an electrically continuous sheet and all the myocytes to be activated simultaneously

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what are desmosomes?

‘glue’ cells together
specialized adhesive protein complexes that localize to intercellular junctions and are responsible for maintaining the mechanical integrity of tissues

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describe the structure of desmosomes

glycoproteins called cadherins span the 25nm gap between the cell membranes
desmin forms the intermediate filaments

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label this diagram

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what is the sarcolemma?

membrane surrounding the cardiomyocyte

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what structures does the sarcolemma also dip into?

T-tubules

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what provides a ready supply of ATP to sustain contraction?

mitochondria

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name 2 contractile proteins

actin

- myosin

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what is the name of the essential contractile unit of a cardiomyocyte?

sarcomere

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what are sarcomeres made up of?

actin and myosin

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how many sarcomeres roughly are there end-to-end in a cardiomyocyte?

around 50

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what are Z lines attached to?

the thin filaments = actin

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what do the thin filaments form a sandwich with?

myosin thick filaments

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label this sarcomere

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what is the A band generated by?

myosin thick filaments

what is the I band mainly composed of?

actin thin filaments

what are T-tubules?

= transverse tubules

- invaginations of the cell membrane which run into the interior of the cell

what do t-tubules do and promote?

- transmit the electrical stimulus rapidly into the interior of the cell - promote the synchronous activation of the whole depth of the cell, despite the fact the signal to contract is relayed across the external membrane

in what stage of a contraction do calcium levels peak?

peak in systole, then come back down to baseline in diastole

what is the trigger for contraction?

a rise in intracellular (cytosolic) Ca++ in the cardiomyocyte

what is meant by the term excitation-contraction coupling?

the Ca++ dependent pathway via which electrical activation of the myocyte induces contraction

Ca++ intracellular levels at rest (diastole) vs in contraction (systole)

at rest: 100nM | in contraction: 1uM = MUCH HIGHER

what is an action potential (AP)?

the transient depolarisation of a cell as a result of ion channel activity

the relationship between AP and contraction — explain this diagram (1-5)

1. voltage-gated Na+ channels open 2. Na+ inflow depolarises the membrane and triggers the opening of more Na+ channels — creates a +ve feedback cycle and a rapidly rising membrane voltage 3. Na+ channels close when the cell depolarises, and the voltage peaks at nearly +30mV 4. Ca++ entering through slow calcium channels (L-type) prolongs depolarisation of membrane, creating a plateau — plateau falls slightly because of some K+ leakage, but most K+ channels remain closed until end of plateau 5. Ca++ channels close and Ca++ is transported out of cell. K+ channels open and rapid K+ outflow returns membrane to its resting potential

when the AP is triggered and Ca++ enters the cell, what then happens to induce a contraction?

- Ryanodine receptors open = calcium induced calcium release — calcium can flood out of the sarcoplasmic reticulum, causing this rise in intracellular calcium levels (that we can measure with the calcium transient) - calcium then binds to the contractile machinery and we get contraction of the heart

where are RyRs located?

on the sarcoplasmic reticulum membrane

what needs to occur between filaments in order for a contraction to happen?

cross bridges need to form between filaments

what 3 things is the thin filament composed of?

- actin - tropomyosin - troponin complex — made up of 3 cardiac specific proteins = cTnT, cTnC, cTnI (cardiac troponin)

what is the thick filament composed of?

- myosin - hinged stalk - globular head

what happens when calcium binds to cTnC?

it induces a rearrangement in the troponin-tropomyosin complex

what is the effect of the rearranged of the troponin-tropomysoin complex, leading to contraction?

movement of tropomysoin exposes a myosin binding site on actin, allowing the globular head of the myosin to bind to it, resulting in cross-bridge formation and shortening of the sarcomere —> CONTRACTION

what does the binding of calcium to cardiac troponin c regulate?

the contractile state of the cardiomyocyte

for relaxation to occur what do we need to happen?

calcium levels to come back down to baseline

where does the majority if the Ca++ need to re-enter?

the sarcoplasmic reticulum

what does Ca++ enter the SR through?

a protein called the sarcoplasmic ATPase (SERCA)

what regulates the action of sarcoplasmic ATPase (SERCA)?

an additional protein called phospholamban

where else does Ca++ get transported into and why?

into mitochondria as Ca++ is very important for mitochondrial function

what 2 ways is the equivalent of the Ca++ that entered the cell through the LTCC removed?

- either via the sodium calcium exchange (swaps calcium for sodium) - or it goes out throguh the plasma membrane calcium ATPase (PMCA)

what would the relationship between Ca++, contraction and AP look like on a graph?

DIASTOLE: explain phase 1 and phases 5-7

phase 1: - atrial depolarisation — P wave - both atria contract — ventricles full phases 5-7: - ventricles are relaxed - mitral and tricuspid valves open - blood flows passively from atria into ventricles

what is LVEDV roughly in an adult heart?

120ml

in what stage of the cardiac cycle do the ventricles contain the full amount of blood?

end of diastole

SYSTOLE: explain phase 2 and phases 3-4

phase 2: - AV valves close - ventricles contract, pressure increases, volume unchanged = isovolumetric contraction - ventricular depolarisation = QRS complex phases 3-4: - outflow valves open - blood ejected into aorta and pulmonary artery - volume decreases = LVESV

what is LVESV in an adult heart?

50ml

what is it called when there is no change in volume of blood as all of the valves are shut?

isovolumetric contraction

what ion channel is responsible for the plateau phase of the ventricular AP? why is the plateau relatively stable?

= L-type Ca++ channel - the LTCC is an inward current, so depolarises the membrane in competition with the repolarising K+ channels (outward currents), therefore creating a plateau where the MP is relatively stable

describe what is happening with the cardiac valves at points A, B, C, D

``` A = mitral valve closes — LVEDV B = aortic valve opens C = aortic valve closes — LVESV D = mitral valve opens ```