Excitable tissue, muscle lecture: 3

Question 1

Describe the intercalated discs of cardiac myocytes:

Answer 1

Intercalated discs:
• Desmosomes prevent cells from
separating during contraction
• Contain gap junctions that allow the
action potentials to be carried from
one cell to the next
• Allows for the co-ordinated
contraction of all the myocytes (unlike skeletal muscle where fibres are recruited via the motor nerves)

Question 2

All the mycocytes of he heart are connected, whats the word to describe this:

Answer 2

Syncytium

Question 3

Describe the action potential of the cardiac myocyte: (insert pic)

3 major stages (0,2,3)

Answer 3

0 – Rapid depolarisation due to fast voltage- gated Na+ channel
2 – Plateau phase due to slow voltage gated Ca2+ channel (L-type Ca2+ channel)
3 – Repolaristation due to closing of Ca2+ channels and opening of K+ (outward) channels

Question 4

How does the cardiac AP differ to skeletal?

Answer 4

• Action potential is long lasting > 100 ms long
• Has plateau phase due to presence of a large sustained Ca2+ current (ICaL) (SLOW L TYPE CA CHANNELS)
• Membrane potential depolarised throughout most of the “twitch” (heart beat)
• Summation/tetani of cardiac muscle highly unlikely

Question 5

Whats the absolute refractory period and relative refractory period of cardiac mycoytes?

Answer 5

ARP: ~200ms

RRP:~250ms

Question 6

Describe the major flow of ions during each stage of the cardiac AP:

Answer 6

insert pic

Question 7

What is the structural basis for Excitation contraction coupling in cardiac myocytes:

Answer 7

T tubules contain:

• NCX (removes Na and allows Ca in (to balance and prevent excessive deloparisaiton)
• L type voltage gated Ca channels
• Na/K ATPase

Basically T tubules depolarise with the Sarcolemma, This opens the L type Ca channels (DHPR), Ca flows and binds RyR on the sarcolemma, and this induces Ca release. (the DHPR and RyR are aligned)

Na/K ATPase create the electrical gradient.

Question 8

Describe cardiac muscle excitation contraction coupling:

Answer 8

• Depolarization opens voltage-gated fast Na+ channels in the sarcolemma. Reversal of membrane potential from –90 mV to +30 mV
• Depolarization wave opens slow (L-type) Ca2+ channels in the sarcolemma (DHPR)
• Ca2+ influx balanced by a Na+/Ca2+ exchanger

• Ca2+ influx triggers opening of Ca2+-sensitive channels in the SR (RyRa), which liberates bursts of Ca2+ (i.e. calcium induced calcium release)
RyRa
• The raised intracellular Ca2+ concentration allows
Ca2+ to bind to troponin, which then switches on the contractile machinery (cross bridge cycle)

Question 9

Describe how relaxation occurs in the cardiac mycote:

Answer 9

For relaxation to occur [Ca2+]i must decline, allowing Ca2+ to dissociate from troponin.
This requires Ca2+ transport out of the cytosol by four pathways (in green):
• SR Ca2+-ATPase (SERCA) (majority is this)
• sarcolemmal Na+/Ca2+ exchange (NCX)
• sarcolemmal Ca2+-ATPase (NOT SERCA)
• mitochondrial Ca2+ uniport.

Question 10

What is cardiac output?

Answer 10

Volume of blood pumped out of the heart per a minute

CO = HR x SV

HR = Heart rate
SV = stroke volume, the volume of blood in the ventricle.

Question 11

What determines heart rate

Answer 11

Heart Rate (HR) is set by the pacemaker cells in the sinoatrial node. The rate can then be modified, especially via the autonomic nerves releasing neurotransmitters.

Question 12

What influences stroke volume?

Answer 12

Stroke volume (SV) reflects the tension developed by the cardiac muscle fibres in one contraction. Can be increased by:
• increased rate of firing (heart rate/HR)
• increased stretch of ventricles (length)
• certain neurotransmitters (e.g. Noradrenaline)

Question 13

What are the pacemaker cells of the heart?

Answer 13

Sinoatrial node

AV node (dont need to understand yet, next sem)

Question 14

Describe the action potential of the pacemaker cels:

Answer 14

1. Pacemaker potential: Slow depolarisation is due to funny current (Na drive) (unstable resting membrane potential) (this is not the rapid Na influx usually seen after threshold is reached)
2. Depolarization: At threshold, Ca2+ channels open. Explosive Ca2+ influx produces the rising phase of the action potential, sustained by opening of slow Ca2+ channels. (different from normal as Na usually drives this part)
3. Repolarization is due to Ca2+ channels inactivating and K+ channels opening.

Question 15

Describe the autonomic innervation of the heart:

Answer 15

Autonomic = Autonomic nervous system i.e regulates body without need for any conscious input

Heart:

• Parasympathetic = vagus nerve, releases Ach, slows heart rate
• Sympathetic = cardiac nerves, release noradrenalin increase HR and contractile strength

Question 16

Describe the neural control of the heart again:

Answer 16

Via alteration of pacemaker potential

Vagal nerves release acetylcholine (ACh): Decrease rate of spontaneous depolarization and hyperpolarises the resting membrane potential = decrease heart rate

Sympathetic nerves release noradrenaline (NA): Increases rate of spontaneous depolarization = increase heart rate

Question 17

What is “automacity” in reference to the heart?

Answer 17

• Increasing heart rate increases contractile force (stroke volume)
- due to less time available for Ca2+ to be pumped out of cell

Question 18

What does the length tension relationship look like in muscle?

Answer 18

(just be able to recognise)

insert pic

Question 19

What is notable about the length tension relationship in muscle?

Answer 19

• Increased stretch (ventricular filling=preload) results in more force developed (stroke volume)
• Starlings law of the heart: “as the resting ventricular volume is increased the force of the contraction is increased”
• entirely intrinsic!

i.e when you exercise more blood returns to the heart, it fills to a higher degree and consequently contracts harder, ejecting more blood.

Question 20

Describe the neural influence on stroke volume:

Answer 20

Noradrenaline (NE = NA) acting on β receptors and via second messengers acts on:
• L-Type channels resulting in more calcium entering the cell.
• Ca2+ pump in SR so SR increases its Ca2+ stores

Net result = bigger/shorter contraction

Question 21

Describe again the neural influence on stroke volume but now with reference to action potential phase.

Answer 21

Noradrenaline released by sympathetic nerves leads to increased cytosol calcium due to increased HR shortening time for extrusion
And via second messengers (previous slide) :
- by increasing Ca++ influx (via Ca++ channels) during the action potential (primarily during phase 2),
- by increasing the release of Ca++ by the sacroplasmic reticulum (due to greater SR uptake)
Increased sympathetic stimulation results in increased output at any filling pressure due to increase in inotropy and heart rate

Question 22

Compare and contrast the conductivity of skeletal and cardiac muscle:

Answer 22

Skeletal : Electrically isolated

Cardiac: electrically coupled (intercalated discs, syncitum)

Question 23

Compare and contrast the trigger for Ca release from the SR in skeletal and cardiac muscle:

Answer 23

Skeletal = Na

Cardiac = Ca

Question 24

Compare and contrast how Ca and recruitment of more fibres influences contraction in skeletal and cardiac muscle:

Answer 24

Skeletal: (Ca) Contraction is always all or none (troponin always saturated). Recruitment of more fibres (yes) contraction always graded

Cardiac: (Ca) Contraction graded, troponin not saturated. (cant recruit more fibres as all fibres or none)