Lecture 3: Cardiac muscle physiology 1

Question 1

What is the main type of metabolism in myocytes?

Answer 1

Mainly oxidative metabolism

Question 2

In the myocardium what is the main cell types?

Answer 2

Cardiac fibroblasts (Majority)
Myocytes (30%)
- Majority of mass
Endothelial cells
Vascular smooth muscle cells
Neurons

Question 3

Describe the appearance of myocardium longitudinal section;

Answer 3

Striated
EC space collagen filled
Intercalated discs at intracellular junctions, consists of;
- Nexus / gap junctions
- Fascia adherins
- Macula adherens (desmosomes)

Question 4

Brief overview of myocyte structure

Answer 4

Sarcolemma: Continuous with T-tubules, contains ion channels

T-tubules at Z disc, Rich in L-type Ca channels (DHPR)

Sarcolemma-SR junctions (Lego hand shape, SR doesnt wrap entirely around), RyR

SR- RyR, SERCA, Calsequestrin, Phospholambam

Question 5

What is EC coupling?

Answer 5

Excitation-contraction coupling

Question 6

Describe EC coupling stages;

Answer 6

1. Activation of Ica (L type Ca channels)
2. Ca induced Ca release (SR RyR)
3. Force development

Question 7

Describe what changes L-type Ca channel function

Answer 7

• Stimulated by catecholamines
• Inhibited by Ca channel blockers and Mg
• Inhibited by low plasma Ca and vice versa

Question 8

Write some notes on SR;

Answer 8

Reservoir of Ca

• Ca buffered in SR by calsequestrin
• 35-40Ca ions per calsequestrin

SR Membrane contains;

• RyR channels at junctional SR
• SR Ca ATPase (SERCA) regulated by phospholambam

Question 9

What happens when SR Ca is high?

Answer 9

• Increased Ca available for release

- Enhanced gain of EC coupling (fraction of Ca release for any given ICa trigger)

Question 10

What regulates RYR2?

Answer 10

Many things including Ca

Question 11

Describe Ca cycling;

Answer 11

SERCA -> Uptakes plasma Ca and NCX
CICR trigger
RYR2 opens and Ca release
High plasma Ca closes RYR2

Question 12

Describe EC coupling;

Answer 12

• AP from adjacent cell spreads across SL.
• Depolarisation opens L-type Ca channels (DHPRs)
• Ca influx opens RYR causing SR Ca release
• Ca ions bind to TnC and initiate crossbridge cycling

= Contraction

Question 13

Describe myocyte relaxation;

Answer 13

• Occurs when [Ca]i is reduced, and Ca unbinds from TnC
• Bulk of Ca is pumped back into SR for storage, NCX takes Ca out of cell
• [Na]i gradient maintained by Na/K ATPase

Question 14

What are the four important Ca exchangers in myocyte relaxation?

Answer 14

• SERCA
• Ca ATPase (out of cell)
• NCX (out of cell)
• Mitochondrial Ca uniporter (into mitochondria)

Question 15

In steady state what is the flow of Ca?

Answer 15

• Steady state Ca influx = efflux

Question 16

What must occur in order for relaxation?

Answer 16

Intracellular Ca must be restored to resting (diastolic) levels

Question 17

How is Ca restored?

Answer 17

1. Muscunaric (Ach) driven CaATPase at the sarcolemmal membrane
2. NCX (Forward mode) - This removes Ca that mainly entered via L-type Ca channels. (Reverse mode during early AP can contribute to Ca influx)
3. SERCA and Ca mitochondrial uniporter

Question 18

Describe myocyte relaxation: (specific wording)

Answer 18

• Occurs when iCa is reduced, and Ca unbinds from TnC
• BULK of Ca is pumped back in SR for storage and SMALL amount leaves cell via NCX
• iNa gradient maintained by Na/K ATPase

Question 19

What happens if Ca efflux is decreased? or Ca influx is increased?

Answer 19

• If Ca efflux is decreased
  1) Higher SR Ca
  2) increased Ca efflux to balance the influx.

If Ca influx increases these will both occur also

Ca regulates extrusion to always try maintain Ca balance

Question 20

Do we care about the SL Ca ATPase?

Answer 20

Not really as no drugs target it and its very slow, minor contributor to Ca extrusion

Question 21

Describe the contribution of NCX to Ca extrusion: and what stimulates its activity.

Answer 21

Ca extrusion (Forward mode) depends on electrochemical gradient.

• Stimulated by low iNa, high Ca and -ve membrane potential

Question 22

Describe the contribution of NCX to Ca influx: and what stimulates it

Answer 22

Ca influx depends on electrochemical gradient

• Stimulated by high iNa, low iCa, and more +ve membrane potential.

Question 23

Describe the Ca cycle across the SL during depolarisation:

Answer 23

• DHPRs contribute to most of Ca plateau

- NCX contributes to maintained Ca plateau and then switches to forward mode during early repolarisation