In the SR, calcium is bound to a protein: 1. What is this protein called? 2. What affinity to calcium does it have and what does this mean? 3. What does this allow?

1. calsequestrin 2. low affinity but high capacity - it can store a lot of calcium without binding to it too tightly 3. allows rapid release during each heartbeat

CVS 4 Flashcards by Alyssa Conte

What does the term ‘automacity’ mean in regards to the pacemaker cells of the heart?

the pacemaker cells of the heart have the intrinsic ability to spontaneously depolarise and trigger action potentials

their action does not require extrinsic input

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Label the image.

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What cells intrinsically initiate ion-dependent electrical events at regular intervals (60-80 per minute)?

pacemaker cells/non-contractile nodal cells

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What do pacemaker/non-contractile nodal cells do?

they intrinsically initiate ion-dependent electrical events at regular intervals (60-80 per minute)

(they spontaneously depolarise thanks to funny ion channels, Ca2+ influx and K+ efflux = automatic electrical activity does not need nerves telling them what to do)

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Describe the pathway of electrical impulse propagation through the heart that leads to ventricular contraction.

ion-dependent electrical impulses propagate from the SA node to the AV node via the intraventricular septum
intraventricular septum to cardiac apex

this initiates contraction of the contractile cardiomyocytes

this spreads through the myocardium to produce a co-ordinated heartbeat

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Through which structure do impulses travel from the AV node towards the ventricles?

Where do impulses go after passing through this?

via the interventricular septum (through the bundle of His and bundle branches)

cardiac apex

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What is the difference between depolarisation and repolarisation?

What does ‘atrial depolarisation’ mean?

depolarisation: start of the impulse (electrical activation)

repolarisation: the reset (recovery)

atrial depolarisation: atria’s muscle cells are being electrically activated so they can contract

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What is happening in each step?

P wave = SA node fires, atria depolarises -> atria contracts
pause at AV node, gives atria time to finish squeezing blood into the ventricles before ventricles contract
QRS complex = ventricles depolarise -> starts at apex and spreads upwards / atrial repolarisation happens at same time
ventricles fully depolarise
T wave = ventricles repolarise, starts at apex again, then spreads -> ventricles relax
ventricular repolarisation complete = heart is fully reset and ready for the next beat

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Label the image of this cardiomyocyte.

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How does cardiomyocyte contraction occur?

force generated by contractile apparatus - ACTIN-MYOSIN

normally tropomyosin blocks actin’s binding sites, when intracellular calcium rises, calcium binds to troponin -> move tropomyosin aside -> myosin can attach to actin

myosin does a “power stroke” -> stroke pulls actin filament towards centre (M-line) of sarcomere

force = PROPORTIONAL TO CALCIUM, higher the Ca2+ -> the more cross-bridges can cycle -> more bridges = more tension (pulling force)

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How many types of troponins are there? What are they and which one does calcium bind to?

3 types:
- troponin T (tropomyosin binding)
- troponin I (inhibitory protein)
- troponin C (calcium binding)

calcium binds to cTnC

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What determines cardiomyocyte contraction/relaxation?

internal calcium (Ca2+)

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Why must Ca2+ rise and fall?

rise: to allow cardiomyocyte contraction during systole (ventricles squeeze)

fall: to all cardiomyocyte relaxation during diastole (heart muscles relax and ventricles fill with blood)

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What is the purpose of Gap Junctions?

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How does calcium enter cardiomyocytes to trigger contraction?

DEPOLARISATION SPREADS ACROSS MYOCARDIUM
- SA node fires and generates action potential, electrical signal moves across atria and ventricle
VGCCs
- gates in cell membrane that respond to changes in membrane voltage = they open when cell becomes LESS NEGATIVE (depolarise)
CALCIUM INFLUX
- when VGCCs open, Ca2+ flows from extracellular space into cardiomyocyte
- rise in intracellular calcium is the SIGNAL THAT TRIGGERS CONTRACTION

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Where is calcium stored?

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Where does calcium come from for cardiac contractions to occur?

outside the cell through VGCCs
inside the cell, stored in the sarcoplasmic reticulum

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Where is rapidly-releasable calcium stored?

in the intracellular stores in the SR

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When Ca2+ enters the cell from outside through VGCCs, it triggers channels on the SR membrane to open.

What are these channels called and what is the mechanism of action?

ryanodine receptors (RyRs)

influx of Ca2+ through VGCCs triggers RyRs to open -> Ca2+ floods out of the SR -> binds troponin -> contraction starts

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What is calcium-induced calcium release (CICR)?

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Where is Ca2+ concentration lowest and where is it highest? Why?

highest: inside SR
lowest: cytosol

this gradient ensures calcium flows into the cytosol when RyRs open, driving contraction

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What is the purpose of the SERCA pump? What does this allow?

SERCA = SR Ca2+ - ATPase pump

pump that uses ATP to pump Ca2+ back into the SR after contraction - allows heart to relax (diastole) and refill

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In the SR, calcium is bound to a protein:

What is this protein called?
What affinity to calcium does it have and what does this mean?
What does this allow?

calsequestrin
low affinity but high capacity - it can store a lot of calcium without binding to it too tightly
allows rapid release during each heartbeat

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To relax the heart, cytosolic Ca2+ must drop. What are the two routes by which this occur?

SERCA pump - pumps Ca2+ back into SR for storage
plasma membrane Ca2+ pumps / Na+-Ca2+ exchanger - expels some Ca2+ from cell to extracellular space

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Fill in the gaps: In CICR, Ca2+ acts as an __1__ of the __2__ receptor. Explain what this means.

1. agonist (meaning it activates the receptor) 2. ryanodine - Na+ depolarisation wave causes VGCCs to open, small amount of Ca2+ enters cytosol from extracellular space, this activates RyRs on the SR - RyRs channels release much larger amount of Ca2+ from SR into cytosol - rise in cytosolic Ca2+ causes binding of Ca2+ to troponin C on thin filaments -> tropomyosin moves off actin -> myosin-actin cross-bridges can form -> contraction occurs

1. What are cell membranes charged by? 2. Electrical current in biological systems is carried by what?

1. movement of ions across them 2. ions

What maintains the high Na⁺ outside and high K⁺ inside the cell?

the Na+/K+ ATPase pump (3 Na+ out and 2 K+ in using ATP)

Why is the resting membrane potential closer to K⁺’s equilibrium potential than Na⁺’s?

because the membrane is more permeable to K+ at rest due to K+ leaky channels

What force drives K+ out of the cell at rest?

its concentration gradient (high inside and low outside)

What pulls K+ back into the cell at rest?

the electrical gradient (negative inside the cell)

1. Why is the Na+ gradient important? 2. Why is the K+ gradient important?

1. it drives depolarisation during the action potential 2. it sets the negative resting potential and helps repolarize the membrane after an action potential

At the resting membrane potential, what is the charge inside the cell and why?

What is the resting membrane potential of myocardial fibres?

Each ion has an equilibrium potential. What is this?

hypothetical membrane potential that would develop if that ion were the only ion that could cross the membrane

What is the equilibrium potential of the following: a. Potassium ions (K+) b. Sodium ions (Na+) c. Chloride ions (Cl-) d. Calcium ions (Ca2+)

a. -90mV b. +50mV c. -90mV d. +125mV

What is the resting membrane potential determined by?

by which ions can cross the plasma membrane (therefore if the permeability of the membrane to different ions changes, then the membrane potential will change accordingly)

Ions cross membranes via channels, list the 2 features of those channels. Ion channels are gated. What 2 types of gated channels are there?

1. ion selective, 2. can open and close voltage-gated ligand-gated

In diastole, the cell membrane of myocardial cells is most permeable to which ions? What does this mean in regards to the membrane potential?

K+ membrane potential is close to the K+ equilibrium potential (during diastole - resting phase - myocardial cells are not firing an action potential, at rest the membrane has lots of open K+ leak channels which means its more permeable to K+ than Na+ or Ca2+ = RESTING MEMBRANE POTENTIAL "LEANS HEAVILY" TOWARD THE K+ EQUILIBRIUM POTENTIAL)

The initial depolarisation to a threshold opens what channels? What does this mean for the membrane potential? How does this occur?

fast voltage-gated sodium channels - membrane potential moves towards the sodium equilibrium potential and depolarises further = opens all remaining fast sodium channels ventricular cells are stimulated by spread of electrical activity from pacemaker cells - this DEPOLARISES the cells (makes the cell less negative intracellularly) - VGNa channels open quickly - reaches a 'threshold'

What is causing the dip represented by the yellow line? As a result of this what should happen but DOES NOT? Why?

influx of potassium (K+ channels open) it would make the membrane potential repolarise quickly but it does not because voltage-gated calcium channels open - THESE ARE LONG ACTING AND STAY OPEN FOR SOME TIME

What opens the voltage-gated sodium channels? What happens when these channels open?

the initial depolarisation to a threshold (something e.g pacemaker current bringing the membrane potential up to a threshold) Na+ rushes in and membrane potential becomes less negative = depolarisation accelerates = more depolarisation means more Na+ channels open = RAPIDLY DRIVES INSIDE OF CELL TOWARDS Na+ EQUILIBRIUM

How long do calcium channels stay open for? Cell contraction is sustained for what phase of the cardiac cycle? Eventually the Ca2+ channels close, this allows the membrane to do what? What happens at the same time?

250ms systole repolarise - extra potassium channels open which makes the cell repolarise faster - as it does, calcium is sequestered within the cell, so Ca2+ falls and cell relaxes (diastole)

Open calcium channels allow calcium ions into the cell, what does this do? What does this allow?

stimulates release of calcium from the SR (calcium induced calcium release) resulting elevation in Ca2+ allows actin-myosin interaction and cardiomyocyte contraction

Where are pacemaker cells found? What is special about them?

SA node and AV node they can generate action potential spontaneously

The pacemaker action potential is due to what? What do pacemaker cells not have? The upstroke of their action potential is due to what?

slow influx of sodium, "drifts" up fast sodium channels VG calcium channels - SLOW

Why is the action potential of pacemaker cells short and triangular?

Why do pacemaker cells not have a stable resting potential?

because once pacemaker action potential has ended, hyperpolarisation opens HYPERPOLARISATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED (HCN) CHANNELS (funny channels) this turns on a slow Na+ conductance

What channels are referred to as "funny" and why?

hyperpolarisation-activated cyclic nucleotide-gated channels (HCN) - because they open during hyperpolarisation, not depolarisation creates a slow, spontaneous depolarisation

The slow depolarisation caused by HCN channels is called what?

pacemaker potential

What is the pacemaker potential?

the slow depolarisation caused by HCN channels

The pacemaker potential gradually becomes less negative until it reaches what? What does that trigger? What happens next?

threshold - action potential pacemaker potential reaches the threshold to open the voltage-gated calcium channels -> new action potential begins spontaneously

The interval between beats depends on what?

on how fast the pacemaker potential depolarises

In regards to 'control of heart rate', fill in the gaps on the image.

What ion channel/transporter involved in regulating ion movement in cardiomyocytes does digoxin target?

Na+/K+ ATPAse

What is an ECG used for?

used to record electrical activity of the heart from different angles to both identify and locate pathology

On an ECG, what does the P wave represent? Answer the following questions: 1. A tall and peaked P wave could indicate what? 2. A wide (>120ms) and notched ("M" shaped) P wave could indicate what? 3. No distinct P wave could indicate what?

atrial depolarisation (atria contracting) 1. right atrial enlargement (could be due to pulmonary hypertension, tricuspid valve disease, chronic lung disease) 2. left atrial enlargement (could be due to mitral valve disease, hypertension) 3. AF (many causes inc HTN, heart disease, age)

What does the QRS complex represent on an ECG?

ventricular depolarisation (ventricles contracting) - big spike because ventricles are stronger and make more electricity

What does the ST segment on ECGs represent? What happens during this phase?

phase 2 of ventricular action potential: plateau phase of repolarisation (ventricular myocytes are depolarised but not yet repolarising fully) calcium ions enter cell through L-type calcium channels, potassium efflux partially counterbalances it = keeps membrane potential relatively stable which creates the plateau

What does ST elevation indicate? What does ST depression indicate?

elevation: MI (STEMI) depression: NSTEMI, myocardial ischaemia, digoxin effect

What does the T wave represent on ECGs? What does a tall, peaked/tented T wave represent?

final rapid repolarisation - K+ continues to efflux - membrane potential returns to resting level hyperkalemia

What must be present for an ECG to show sinus rhythm?

P wave before each QRS complex

How do you calculate ECG rate?

What method for calculating ECG rate would you use for irregular rhythms?

What is the normal duration of the QRS complex?

< 3 small squares < 120ms (usually 0.06-0.10 / 60-100ms)

What is the normal values for QTc range? What does a value of >500ms suggestive of?

350-440ms for men 350-460ms for women (9-11 small squares) torsades de pointes

CVS 4 Flashcards

(65 cards)