Cardiovascular 3.2 Flashcards

1
Q

What is the role of the pacemaker cells of the heart?

“Automaticity”

A

Automacity
-Pacemaker cells have instrinsic ability to spontaneously depolarise and generate action potentials
-Process occurs without need for external (extrinsic) input from the nervous system

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2
Q

1) What is the role of non-contractile nodal cells?
2) Where to the electrical impulses propogate after being generated in the SA node?
3) What is the role of electrical impulses in cardiac contraction?
4) How does the electrical impulse spread through the heart?

A

Intrisically, initiate ion-dependent electrical events at regular intervals 60-80 per minute

2) Propogate from SA node to AV node, then through intraventricular septum to cardiac apex

3) Initiate contraction of contractile cardiomyocites

4) Spreads through myocardium, producing coordinated heart beat

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3
Q

1) What generates force during cardiomyocyte contraction
2) What triggers tenstion generation in cardiomyocytes
3) How is the amount of tension related to intracellular calcium levels

FOCUS ON CA2+ binds to cTnC

A

1) Contractile apperatus, involving actin and myosin

2) Tension generated when intracellular calcim levels rises

3) Tenstion is proportional to (Ca2+)i concentration

cTnC - Cardiac Troponin C, initiates process of muscle contraction in cardiomyocoytes

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4
Q

1) What role does intracellular calcium ions play in cardiomyocyte contraction?

2) What role does (Ca2+)i play in cardiomyocyte relaxation?

A

1) (Ca2+)i must rise during systole to allow cardiomyosyte contraction

2) Must fall in diastole to allow relaxtaion

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5
Q

1) How is [Ca²⁺]i elevated inc cardiac myocytes?

2) How is [Ca²⁺]i returned to basal levels in cardiac myocytes?

A

1) Elevated by calcium influx through L-type calcium channels during depolarisation

2) Calcium efflux via sodium calcium exchanger (NCX) and calcium reuptake into sarcoplasic reticulum by SERCA pumps

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6
Q

1) What do voltage-gated Ca2+ channels (VGCCs) do?

A

Influx of Ca2+ into cells by opening in response to depolarisation (increase in membrane potential)

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7
Q

1) What channels release Ca2+ from intraceullar stores in cardiac cells?

2) What is the function of SERCA pump?

3) Which protein stores Ca2+ in sarcoplasmic reticulum?

A

1) Ca2+ release channels (e.g. ryanodine recepors). e.g. of intracellular store = sarcoplasmic reticulum

2) stands for (sarco/endoplasmic reticulum Ca²⁺ ATPase) uses ATP to pump Ca2+ back into SER, lowering intracellular Ca2+ after contraction

3) Calsequestrin - lw affinity, high capacity Ca2+ hinding protein

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8
Q

1) What is the process of Ca2+ induced and Ca2+ release CIRC?

2) What is conformational coupling in skeletal muscle, and how does it relate to CICR?

A

1) Calcium influx from VGCC triggers release of further calcium from SER through ryanodine receptors. Inrease in intracellular calcium leads to muscle contraction. SERCA then returns calcium back to SER to end contraction

2) In skeletal muscle, conformational coupling occurs between VGCC and RyR. Unlike, cardiac muscle, Ca2+ influx triggers CICR, in skeletal muscle, the physical. interaction (conformational coupling) between these channels initiates calcaium release form RER without requiring VGCCs

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9
Q

How does Ca2+ act as an agonist in CICR through RyR?

A

ca2+ bind to RyR on SR, This triggers, further Ca2+ release from SR, leading to increased intracellular Ca2+ levels + contraction of contractile proteins (actin, myosin)

Depolarisation driven by Na+, Ca2+ influx by VGCC in T tubules initiates this process.

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10
Q

1) What role does the Na+/Ca2+ (NCX) pkay in cardiac myocytes?

A

1) NCX removes Ca2+ from cell during relaxation by exhancing 3Na+ ions for 1 Ca2+ ion, allowing cell to relax after contraction

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11
Q

1) What casues elevated ([Ca²⁺]i) in cardiac myocytes?

2) What is an action potential?

A

Elevated [Ca²⁺]i occurs due to an action potential in the cell membrane, which triggers calcium influx.

2) Disturbance of cell membrane potential, causing ion channels to open, initiating calcium release

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12
Q

1) What is the function of the cell membrane in terms of electrical charge?

2) How are membranes charged in biological systems?

What carries electrical current in biological systems?

A

1) Act as capacitors. store electrical cahrge

2) by movement of ions across them

3) ions not electrons

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13
Q

Where are Na+ and K+ concentrations higher in relation to the cell?

A

Na+ - outside cells
K+ - inside cells

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14
Q

What happens to the membrane potential if only k+ can move across membrane?

A

K+ leave cell, taking +ve with them. Causes inside of membrane to become -ve charged as membrane capacitor charges up

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15
Q

1) What happens when equilibrium is reached in terms of K+ movement?

2) What determines equilibrium membrane potential?

3) What is the resting membrane pitential of myocardial fibres?

A

1) No more K+ leaves cell

2) Ratio of K+ conc indide + outside cell

3) -90mV

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16
Q

1) What is the equilibirum potential for an ion?

A

Hypothetical membrane potential that would develop if a particular ion were the ONLY ion to cross membrane

17
Q

1) What determines resting membrane potential?

A

1) Which iones corss plasma membrane. If permeability of membrane to different ions changes, membrane potential changes

18
Q

1) How do ions cross membranes?

2) WHt are two characteristics of ion channels?

3) What are two types of ion-gated channels?

These questions can relate to membrane permeability and what effecst it

A

1) through ion channels
2) ion channels are selective,and can open and close

3)voltage-gated
ligand gated

19
Q

What type of voltage-gated ion channels are found in myocardial cell membranes?

A

Voltage-gated potassium, sodium, calcium channels

20
Q

1) What happens to the membrane potential during diastole in myocardial cells?

2) How are ventricular cells depolarised?

3) What happens when the initial depolarisation reaches threshold?

4) What happens after fast sodium channels open?

5) Wht doesn’t the membrane potential repolarise quickly after sodium channels close?

6) What is the effect of the calcium equilibrium potential

7) How does calcium-induced calcium release occur?

8) How long do calcium channels stay open during the cardiac ction potential?

9) What role do potassium channels play during repolarisation?

A

1) Membrane potential most permeable to K+, making membrane potental close to K+ equilibrium potential

2) Ventricular cells stimulated by spread of electrical activity from pacemaker cells, causing depolarisation (making inside of cell less negative)

3) Fast-voltage gated sodium channels open, causing membrane to depolarise further to Na+ equilibirum potential

4) All remaining fast sodium cahnnels open, making membrane potential positive inside, but these sodium channels close quickly

5) Voltage-gated calcium channels open, preventing rapid repolarisation

6) There is more Ca2+ outside the cell, so the calcium equilibirum potential is posotive inside, and opening of calcium channels keep the membrane depolarised]

7) Open calcium channels allow Ca2+ into cell, which stimulates release of calcium from sarcoplasmic reticulum, leading to actin-myosin interactions and cardiomyocyte contraction

8) 250ms, sustaining contraction during systole, when they close, membrane starts to repolarise

9) Extra potassium channels open, speeding up repolarisation, while calcium is sequestered within cell, causing [Ca²⁺]i to fall and the cell to relax during diastole.

21
Q

1) Where are pacemaker cells found, and what is their function?

2) State an example of non-contractile nodal cells

A

1) Pacemaker cells are found in SAN and AVN.

They generate action potentials spontaneously without external stimulation

2) pacemaker cells

22
Q

State and explain 2 key differences between the cardiac action potential and pacemaker action potential

A

1) No fast sodium channels
- Pacemaker cells lack fast sodium channels
-Upstroke of their action potential is due ot calcium channels, which make upstroke slow compared to other action potentials

2) Short, triangular action potential
-Calcium ion channels in pacemaker cells close quickly
-So, AP in pacemaker cells short + triangular in shape

23
Q

What happens once pacemaker action potential ends?

A

Hyperpolarsiation opens. Hyperpolarisaion-acivtaced clyclic nucleotide gated (HCN) channels

This turns on slow Na+ conductance

Leads to membrane potential not being stable, preventing it from staying at rest

Depolarises slowly due to hyperpolarisation cahnnels, which are permeable to both Na+, K+

This creates H currents (funny currents), due to unusual activation pattern

The pacemaker potential refers to the slow drift of depolarisation towards threshold. Once the membrane potential reaches threshold, voltage-gated calcium channels open

24
Q

Control of heart rate

1) What determines the inerval between heart beats?

2) How does sympathetic action affect pacemaker potential and heart rate?

3) How does parasympathetic action affect pacemaker potential and heart rate?

A

1) How fast pacemaker potential depolarises

2) Speeds up heart rate by increasinf rate of pacemaker potential depolarisation

3) Slows down heart rate by decreasing rate of pacemaker potential depolarisation

25
Q

1) How does noradrenaline affect heart rate?

2) How does aceytlcholine affect heart rate?

A

1) Speeds up HR by making pacemaker potential steeper, increasing rate of depolarisation

2) Slows down heart rate by making pacemaker potential shallower, decreasing rate of depolarisation

26
Q

What does an electrocardiogram represent (ECG)?

A

Extracellualrly recorded sum total of electrical activity of all individual cells of the heart

27
Q

How do drugs like digoxin treat heart failure?

A

target ion channels and transporters involved in regulaiing ion movement in cardiomyocytes.

Digoxin specifically targets Na+/K+-ATPase

28
Q

What are the steps involved in the generation of a cardiac action potential? (8 marks)

A

Cardiac Action Potential

Diastole of myocardial cells. Membrane potential most permeable to K+. Close to K+ equilibrium potential
Ventricular cells depolarised: Ventricular cells stimulated by spread of electrical activity from pacemaker cells
Initial depolarisation reaches threshold: Fast voltage-gated Na+ channels open, membrane depolarises further. Close to Na+ equilibrium potential
All remaining fast voltage gated Na+ channels open. More depolarisation. However, close quickly
VGCC open. Prevent rapid repolarization. Keeps membrane depolarised
VGCC = CICR. Actin + myosin interactions = cardiomyocyte contraction (250ms sustaining contraction during systole)
VGCC stay open 250ms, sustain contraction during systole, VGCC then close, membrane starts to repolarise
Extra potassium channels open, speed up repolarisation. Calcium is sequestered within cell, causing intracellular Ca2+ to fall + cell to relax in diastole