Cardiac Physiology

Question 1

What is membrane potential

Answer 1

In most cells types there is an electrical potential difference between the inside of the cell and the surrounding extracellular fluid. This is termed the membrane potential of the cell

Question 2

Cell in rest

Answer 2

• When a cell is at “rest”, its membrane potential is called the resting membrane potential; in most cells this is negative i.e. the cell is negative with respect to the outside

Question 3

Non excitable cells

Answer 3

• In non-excitable cells, the resting potential does not change much over time

Question 4

• Sinoatrial node cells do not typically have a stable resting potential (but is around -60 mV)

Question 5

In excitable tissues

Answer 5

• In excitable tissues, like neurons and muscle, stimulation of the cell results in a ‘big’ change in potential, over a short period

Question 6

An action potential

Answer 6

an action potential – that brings about a functional response
• Nerve impulse
• Contraction of muscle

Question 7

The action potential

Answer 7

is generated by rapid changes in electrochemical gradients across the cell membrane;

Question 8

movement of ions into and out of the cell

Answer 8

Chemical gradient – ion will move down its [gradient]
• Electrical gradient – ion will move away from like charge

Question 9

Movement is controlled by specific ion channels embedded in the cell membrane like

Answer 9

• notable channels/ions = K+, Na+ and Ca2+

Question 10

Movement of ions generate characteristic changes in potential differences; transmembrane potential (mV)

Answer 10

Depolarization – less negative (becomes positive in muscle)
• Repolarization – a return to the negative resting potential
• Hyperpolarization – become more negative with respect to
typical resting potentials

Question 11

Heart muscle consists of

Answer 11

cardiomyocytes or myocardial fibres

Question 12

Heart muscle

Answer 12

• Around 20 x 100 M and branched
Rich in mitochondria 5000-8000 / cell
• Numerous Ion channels and pumps

Question 13

Fibres

Answer 13

Formed by individual cells joined end-to-end by specialized junctions – intercalated discs

• Ensure tight interactions and mediate electrical coupling
• Fibres often branch to extend the interconnections
• Single central nucleus and an abundance of mitochondria

Question 14

Cells show a repeating pattern of striations, which are the actin and myosin filaments (plus several other proteins)
• Filaments slide along each other to facilitate contraction
• Contraction is dependent on by calcium signalling
Diagram to illustrate cardiomyocyte structure •
•
Contractions synchronized via the intercalated discs and gap junctions between them; this ensures that individual cardiomyocytes work together and the cardiac muscle functions as a syncytium

Question 15

Sinoatrial node propagates the

Answer 15

action potential

Question 16

How Sinoatrial node propagates the action potential

Answer 16

• Excites the right atrium, then left atrium via the Bachmann’s bundle
• Reaches atrioventricular node via right atrium
• Intrinsic rhythm is 60-100 beats/minute

Question 17

Electrical signalling pathways

Answer 17

Sinoatrial node propagates the action potential

Atrioventricular node passes the signal to bundle of His

This ordered sequence of conduction from atria to ventricles coordinates the specific contraction of the heart chambers ‘

The membrane action potentials of the SA node are different from the contractile myocardial cells

Unstable membrane potential = automaticity of SA i.e., it sets the pace of the heart – the pacemaker

Question 18

AVN has pacemaker potential——— also ——-between atrial and ventricular conduction

Answer 18

(20-60 bpm);

gate keeper

Question 19

Bundle of His Branches to form

Answer 19

right bundle and left bundle

Question 20

What project into and spread
throughout myocardium

Answer 20

Bundles terminate in Purkinje fibres

Question 21

Atrioventricular node passes the signal to bundle of His

Answer 21

Depolarize the right and left ventricle

Question 22

Autorhythmic Cells (Pacemaker Cells)

Answer 22

Undergo spontaneous depolarization when a threshold voltage reached
• Unstable membrane potential, which never falls below -60mV
• Transmembrane potential drifts upward to -40mV, forming a threshold or pacemaker potential
• Slow leakage of K+ out and faster leakage of Na+ into cell
• Causes slow depolarization
• Occurs through If channels (f=funny) aka hyperpolarization-activated cyclic nucleotide-gated (HCN) channels;
these open at negative membrane potentials and start closing as membrane approaches threshold potential
• At -55 mV T-type Ca2+ channels (transient opening) open and continue slow depolarization as membrane approaches threshold
• At threshold potential (-40mV), L-type Ca2+ channels (long lasting) open causing more rapid depolarization to 0 mV, then cause ‘overshoot’ up to ~ +20-30 mV; these deactivate shortly after
• Slow or delayed rectifier K+ channels open as membrane depolarizes causing an efflux of K+ and a repolarization of membrane back to -60 mV
10

Auto-rhythmic Cells (Pace

Question 23

Action potential of the cardiomyocytes (contractile system) composed of what

Answer 23

Composed of 5 distinct phases (0-4); have a stable resting phase unlike the SA node

Question 24

Phase 4: The resting phase

Answer 24

The resting potential in a cardiomyocyte is −90 mV due to a constant outward leak of K+ through inward rectifier channels
• Na+ and Ca2+ channels are closed at resting transmembrane potential (TMP)

Question 25

Phase 0: Depolarization

Answer 25

An action potential triggered in a neighbouring cardiomyocyte or pacemaker cell causes
the TMP to rise above −90 mV
• Fast Na+ channels start to open and Na+ enters he cell, further raising the TMP
• TMP approaches −70mV, the threshold potential in cardiomyocytes, i.e., the point at which enough fast Na+ channels have opened to generate a self-sustaining inward Na+
current
• The large Na+ current rapidly depolarizes the TMP to 0 mV and slightly above 0 mV for a
transient period of time called the overshoot; fast Na+ channels close (fast Na+ channels
are time-dependent)
• L-type (“long-opening”) Ca2+ channels open when the TMP is greater than −40 mV and
cause a small but steady influx of Ca2+ down its concentration gradient.

Question 26

Phase 1:

Answer 26

Early repolarization
• TMP is now slightly positive
• Some K+ channels open briefly and an outward flow of K+ returns the TMP to
approximately 0 mV.

Question 27

Phase 2: The plateau phase

Answer 27

L-type Ca2+ channels are still open and there is a small, constant inward current of Ca2+. This becomes significant in the excitation-contraction coupling process
• K+ leaks out down its concentration gradient through delayed rectifier K+ channels
• These two counter-currents are electrically balanced, and the TMP is maintained at a
plateau just below 0 mV throughout phase 2

Question 28

Phase 3:

Answer 28

Repolarization
• Ca2+ channels are gradually inactivated
• Persistent outflow of K+, now exceeding Ca2+ inflow, brings TMP back towards resting
potential of −90 mV to prepare the cell for a new cycle of depolarization.
• Normal transmembrane ionic concentration gradients are restored by returning Na+ and Ca2+ ions to the extracellular environment, and K+ ions to the cell interior

Question 29

The pumps involved include the sarcolemmal Na+-Ca2+ exchanger, Ca2+-ATPase and Na+-K+-ATPase 13
•
Action potential of the cardiomyocytes (contractile system)

Question 30

Refractory period/plateau

Answer 30

Cardiomyocytes have a longer refractory period than other muscle cells; the plateau from slow Ca2+ channels (phase 2)

Question 31

Physiological mechanism allow

Answer 31

sufficient time for the ventricles to empty and refill prior to the next contraction

Question 32

Sarcomere

Answer 32

is the unit of muscle that contracts; many sarcomeres per cell arranged in series

Question 33

Thin filaments composed

Answer 33

protein actin; thick filaments composed of the protein myosin

Question 34

• Z-lines

Answer 34

demark each sarcomere (thin filaments connect to Z-line)

Question 35

• M-Line

Answer 35

defines the middle of sarcomere and middle of thick filament

Question 36

• I band

Answer 36

is a zone around the Z-lines and includes part of two separate sarcomeres. The I band only has thin filaments.

Question 37

H band

Answer 37

is a zone around the M-line

Question 38

A band

Answer 38

is a zone that demarks the length of thick filaments

Question 39

Myosin

Answer 39

thick filaments with globular heads evenly spaced
along their length; contains myosin ATPase.

Question 40

Actin

Answer 40

thin filaments consisting of two strands arranged as
an a-helix, between myosin filaments

Question 41

Tropomyosin

Answer 41

double helix that lies in the groove between actin filaments. Prevents contraction in the resting state by inhibiting the interaction between myosin heads and actin

Question 42

Troponin

Answer 42

complex with three subunits at regular intervals along the actin strands

Question 43

Troponin T (TnT)

Answer 43

ties troponin complex to actin and tropomyosin molecules

Question 44

Troponin I (TnI)

Answer 44

inhibits activity of ATPase in actin-myosin interaction

Question 45

Troponin C (TnC

Answer 45

binds calcium ions that regulate contractile
Cardiac physiology; part three
process

Question 46

Contractile proteins – Ca2+ is a key regulator

Answer 46

Calcium-induced calcium release (CICR) is required for excitation-contraction coupling
• Influx of Ca2+ into myocytes through L-type Ca2+ channels during phase 2 of the action potential is not sufficient to trigger contraction of myofibrils; signal is amplified by CICR, which triggers much greater release of Ca2+ from the sarcoplasmic reticulum
• The cell membrane of cardiomyocytes, called sarcolemma, contains invaginations (T-tubules) that bring L-type Ca2+ channels into close contact with ryanodine receptors, specialized Ca2+ release receptors in the sarcoplasmic reticulum (SR)
• When Ca2+ enters the cells through L-type channels, ryanodine receptors change conformation and induce a larger release of Ca2+ from abundant SR store
• Large levels of intracellular Ca2+ act on tropomyosin complexes to induce myocyte contraction.

Question 47

 Initiation

Answer 47

action potential via pacemaker cells to conduction fibers

Question 48

Excitation

Answer 48

Contraction Coupling
 Starts with CICR (Ca2+ induced Ca2+ release)
 Action potential spreads along sarcolemma
 T-tubules contain voltage-gated L-type Ca2+ channels
which open upon depolarization
 Ca2+ entry opens RyR (ryanodine receptors) Ca2+ release channels
 Release of Ca2+ from SR causes a Ca2+ release
 Calcium binds troponin C and mediates contraction

Question 49

Contractile proteins – Ca2+ is a key regulator

Answer 49

As with myocyte contraction, the relaxation phase is synchronized with the electrical activity of the cell
• L-type Ca2+ channels inactivate toward the end of phase 2 → Ca2+ influx arrests → CICR trigger is abolished
• Ca2+ is sequestered back into the SR by sarcoplasmic reticulum Ca2+ ATPase (SERCA) and pumped out of the cell to a lesser extent by specialized Ca2+ pumps
• Ca2+ ions dissociate from TnC as intracellular concentration falls, and tropomyosin inhibition of actin-myosin interaction is restored

Question 50

Cardiac muscle, heartbeat and cardiac cycle

Answer 50

• The autonomic system is anatomically and functionally divided into the sympathetic and parasympathetic components
• Sympathetic system stimulates the heart rate
• Stress, exercise, excitement
• Norepinephrine (adrenoceptors)
• Parasympathetic system relaxes/slows the heart
• PNS dominates autonomic stimulation of heart
• Acetylcholine (muscarinic receptors)
• Hormones, local chemical mediators also contribute to control of myocyte activity

Question 51

Autorhythmic Cells (Pacemaker Cells)

Answer 51

Altering Activity of Pacemaker Cells; Sympathetic activity
 Norepinephrine (and epinephrine) increase If channel activity
 Binds to β1 adrenergic receptors which activate cAMP and increase If channel open time  Causes more rapid pacemaker potential and faster rate of action potentials

Question 52

Gap junctions

Answer 52

Gap junctions are intercellular channels 1.5–2 nm in diameter
• Formed by connexin an integral membrane protein; 6 connexin proteins form a connexon or channel, which links with a connexon in neighbouring cell to form the gap junction
• Gap junctions link the cytoplasm of neighbouring cells and enable rapid passage of ions and small molecules
• Permit changes in membrane potential to pass from cell to cell e.g., action potential and sarcomere contraction in the heart

Question 53

regions/structures within the heart comprised of cells that are similar to cardiomyocytes

Answer 53

Sinoatrial and atrioventricular nodes
• The bundle of His and Purkinje fibres

Question 54

SA node also called

Answer 54

SA node also called

Question 55

The heart which originates in the sinoatrial node

Answer 55

intrinsic auto-rhythmicity

Question 56

• Intrinsic waves of excitation (depolarization) spread from the SA node to the AV node and then to myocytes via other parts of the conduction system; the bundle of His and Purkinje fibres
• While capable of functioning independently, the SA is innervated (as are most parts of the heart and circulatory system) by autonomic nerves and SA activity can be controlled by autonomic nervous system signals