Lecture 12

Question 1

Describe the characteristic of the heart being myogenic?

Answer 1

Cardiac muscle contracts without innervation. This allows the heart to be a transplant organ (switched between bodies). Initiated by specialised myocytes in the SA node. Cardiac myocytes elsewhere can generate this type of activity.

Question 2

Can pacemaker activity be initiated somewhere other than the SA node?

Answer 2

Yes. This can be a bad thing particularly in ventricular myocytes - could generate arrythmais.

Question 3

Describe the appearance of cardiac muscle?

Answer 3

It is striated, and the cardiac myocytes are electrically coupled to each other (important for the function of the heart).

Question 4

What is the heart reliant on?

Answer 4

Oxygen.

Question 5

What triggers the contraction?

Answer 5

The AP triggers the synchronised calcium release from the internal store (SR). [CICR].

Question 6

What are the cell types of the heart?

Answer 6

Made up of many different cell types. Cardiac myocytes make up the largest portion of cardiac muscle by volume, they are not the largest number of cells in the heart. Cardiac fibroblasts are the largest number of cells in the heart; their role is to secrete and maintain CT fibres. Myocytes carry out the work of the heart (contraction). There are specialised myocytes which form the purkinje and nodal cells. There are endothelial cells (line the blood vessels and capillaries and the chamber of the hear).

Question 7

Describe the intercalated discs?

Answer 7

There are specialised gap junctions which allow continuity of the cytosol between cells. There are facia adherens and macula adherens (which together form tight connection between cells).

Question 8

Describe the extracellular space?

Answer 8

Makes up about 33% of the heart muscle volume. There are a lot of capillaries in this space - between cardiac myocyte. At each corner of the cardiac myocyte are endothelial cells. Capillaries are associated with every myocyte (important for delivering oxygen to the tissues).

Question 9

Describe the myocyte ultrastructure?

Answer 9

Surface sarcolemma, and invaginations of sarcolemma that form T-Tubule (enable propagation of AP right to the centre of the muscle fibre). The sarcoplasmic reticulum is wrapped around the bundles of contractile proteins.

Question 10

Describe excitation-contraction (EC) coupling?

Answer 10

It is initiated by the AP and the depolarisation of the cell membrane. Changes at the surface membrane lead to changes in the calcium levels. The AP propagates down the T-tubules which causes depolarisation of the membrane (sodium voltage gated channels), this causes opening of the channels, then calcium influx, which triggers greater release of calcium from the SR. Calcium diffuses to the contractile proteins which initiates cross-bridge cycling.

Question 11

Describe the role of DHPR Channels?

Answer 11

They bind the dihyrdipiridine (L type calcium channels). They carry the inward calcium current, contributes to the plateau phase of the ventricular AP, this triggers the excitation contraction coupling. The DHPR responds to SR Calcium release (closed in response to high calcium conc that occurs in gap between junction and SR). When the AP occurs the voltage gated sodium channels open, the depolarisation causes the opening of DHPR. They are stimulated by catecholamines, and inhibited by dihydripiridines.

Question 12

Describe sarcoplasmic reticulum (SR)?

Answer 12

It is the reservoir for intracellular calcium. it’s calcium is buffered in the SR by calsequestrin. It binds 35-40calcium ions per one calsequestrin molecule. In a good healthy mycoyte the calsequestrin has lots of calcium bound to it and it is waiting for a triggered release. The SR membrane contains Calcium release channels and SERCA (takes up calcium to SR during relaxation - diastolic interval between contraction).

Question 13

Describe SERCA?

Answer 13

This is the SR Calcium-ATPase. It has 2calcium:1ATP. It’s function is to reduce calcium levels in the cytosol during relaxation, so it takes calcium back to the SR (diastolic interval

Question 14

What molecule regulates SERCA?

Answer 14

Phospholamban acts to inhibit the uptake of calcium. During high cytosolic calcium, then it loses the inhibitions and enables SERCA to work faster. It is important between beats, that calcium is cleared from the cytosol much faster during exercise.

Question 15

What happens when SR calcium load is high?

Answer 15

There is increased calcium available for triggered release. There is much larger transient of calcium occurring. This is the gain of EC coupling.

Question 16

What happens in failing hearts?

Answer 16

Sometimes the RyRs are a little bit leaky, so they open when they shouldn’t. This depletes the SR, some of the calcium is taken up by SERCA or transported out of the myocyte via the calcium exchange, this can increase the resting calcium level in the cytosol, to a point where contraction keeps occurring. This is known as incomplete relaxation. Diastolic heart failure - inability of mycoytes to relax fully.

Question 17

Describe microscopic SR release events?

Answer 17

They’re called calcium sparks. A fe RyRs open when they shouldn’t and they release calcium. Lots isolated cardiac myocytes to look at the amplitude of the microscopic sparks.

Question 18

Where do the sparks occur?

Answer 18

Within the T-tubule junction

Question 19

Summarise contraction?

Answer 19

AP from adjacent cell spreads across the SL and down the T-Tubules. This will open DHPRs, this will initiate Calcium influx through RyR. This will cause SR calcium release. Calcium bind to TnC and imitate cross-bridge cycling.

Question 20

Summarise relaxation?

Answer 20

Cytosolic calcium level needs to drop rapidly, so calcium unbinds from TnC. The lowering of the calcium is bought about by the SERCA taking up the calcium. For a myocyte to be in steady state, the amount of calcium that comes into the cell via the DHPR must equal the amount leaving via calcium exchange.

Question 21

Describe myocyte relaxation?

Answer 21

There are four important calcium transport proteins: SERCA which puts calcium back into the SR. SL Calcium-ATPase takes calcium out of the cell as well as NCX (SL sodium/calcium exchanger). A mitochondrial uniporter moves calcium into the mitochondria.

Question 22

Describe the balance between calcium extrusion and entry?

Answer 22

At steady state the amount of calcium that goes into the cell must equal the amount that goes out.

Question 23

What happens when calcium efflux is decreased?

Answer 23

Require a higher heart rate, modulate the calcium current, the gain of EC coupling and decreasing efflux. Calcium will accumulate in the cytosol and it is taken up in the SR, thus the next contraction will be greater.

Question 24

What happens when calcium influx is increased?

Answer 24

Calcium will accumulate inside the cell which will lead to a higher SR calcium content and an increased calcium extrusion to balance influx.

Question 25

Describe electrogenic NCX?

Answer 25

Carries one net charge per cycle. Reverse mode brings calcium into the cell. The forward mode is how it normally works during diastole. Sodium/calcium change is important for contributing to the membrane potential.