Cardiac Contraction

Question 1

Describe the structure of cardiomyocytes

Answer 1

Contractile structure, made up of myofibrils which shorten to cause cardiac contraction. The myofibrils are composed of repeating sarcomeres.

Question 2

How do sarcomeres work

Answer 2

Muscle contraction occurs when their actin and myosin filaments move relative to each other

Question 3

What are T tubules

Answer 3

Invaginations of the muscle cell membrane that penetrate into the centre of cardiac muscle cells

Question 4

What is in the cytoplasm between the myofibrils

Answer 4

Nucleus, mitochondria, sarcoplasmic reticulum

Question 5

Describe cardiomyocyte function

Answer 5

Ca2+ enters calcium channel of T tubule, in response to depolarisation. More calcium released from sarcoplasmic reticulum, initiating contraction.

Question 6

Why is the rise in intracellular calcium central to contraction

Answer 6

Calcium stops repolarisation, so levels of Ca2+ inside the cell increase, causing the plateau phase. This causes contraction of the heart muscle and the force of contraction depends on the concentration of the Ca2+ inside the cell at this time.

Question 7

What are striations

Answer 7

Repeated dark bands in cardiac muscle, due to Z lines which mark the junction of actin filaments in adjacent sarcomeres.

Question 8

How does increase in calcium ions cause contraction?

Answer 8

Calcium ions bind to troponin, which is important because it controls the interaction between actin and myosin.

Question 9

What does each troponin subunit bind to

Answer 9

Troponin T binds to tropomyosin
Troponin I binds to actin filaments
Troponin C binds to Ca2+

Question 10

Describe myosin in its high energy form

Answer 10

ADP + phosphate, extends to bind exposed binding site on the actin. Phosphate is released as myosin binds to actin, forming a cross-brdige

Question 11

Describe the power stroke

Answer 11

Myosin changes conformation, releasing its ADP and pulling the bound actin filaments toward the centre of the sarcomere, contracting the muscle. Leaves myosin in low energy conformation.

Question 12

What happens when ATP is bound to the myosin

Answer 12

Myosin released from actin, ATP hydrolysed to ADP + phosphate, ready for new power stroke.

Question 13

How does contraction end

Answer 13

Intracellular Ca2+ actively removed by sarcoplasmic reticulum, dropping Ca2+ conc. Returns troponin complex to its inhibiting position, so myosin cannot bind. Ends contraction, actin filaments return to their initial position, relaxing the muscle.

Question 14

Describe relaxation

Answer 14

1. Voltage gated Na+ channels close, voltage gated K+ begin to open, as each cell enters phase 3 of the cardiac action potential causing repolarisation
2. The repolarisation of the action potential causes repolarisation of the T tubule area and closure of voltage gated Ca2+ channels, Ca2+ is no longer entering the cell. Turns off CICR
3. Na+/Ca2+ exchanger removes calcium from cell in exchange for Na+
4. Majority of intracellular Ca2+ taken back up into sarcoplasmic reticulum, utilises sarcoplasmic reticulum Ca2+ - ATPase, so even the relaxation process uses up a lot of energy. Some taken up by mitochondria

Question 15

How is the Ca2+ effect inotropic

Answer 15

Greater force of contraction with higher intracellular Ca2+ concentration

Question 16

How does Ca2+ affect a typical Starling curve

Answer 16

Shifts curve upwards, as Ca2+ increases force of contraction due to greater ionotropic effect

Question 17

HOw does the sympathetic nervous system control contractility

Answer 17

Noradrenaline acts via Beta-1-adrenoceptors to increase contractility by phosphorylating calcium channels and allowing greater Ca2+ influx, and higher intracellular levels

Question 18

Describe pharmaceutical options for increasing cardiac output.

Answer 18

Two main drug mechanisms - Increasing voltage gated Ca2+ channel activity to increase intracellular Ca2+.

Reducing expulsion of calcium from the cytoplasm, maintaining a higher intracellular Ca2+ for longer

Question 19

Describe mechanism for sympathetic effect on the heart

Answer 19

Beta-1 adrenergic receptors are found on the contractile cells of the heart. Adenylate cyclase catalyses the conversion of ATP to cAMP + 2Pi. The cAMP activates protein kinase A, which phosphorylates the Ca2+ ion channel, causing them to open more easily, so increasing intracellular calcium.

Increased intracellular Ca2+ causes increased calcium induced calcium release, which leads to more binding to troponin C, more actin myosin binding and greater contraction.

Question 20

Describe digoxin action

Answer 20

Inhibition of Na+/K+ -ATPase exchanger. Example of active transport, uses energy from hydrolysis of ATP. For every ATP molecule that the pump uses, three Na+ are exported, two K+ are imported.

Inhibition of this, results in build up of Na+ inside the cell. Reduces Na+ gradient.

Net result of inhibiting the Na+/K+-ATPase exchanger is increased intracellular Ca2+, which increases cardiac contraction and also increase the amount of Ca2+ placed in the sarcoplasmic reticulum store. Greater CICR during depolarisation and greater force of contraction when the next action potential comes alonh.

Question 21

HOw is dobutamine different to noradrenaline

Answer 21

Specifically targets the heart, very weak activity on other types of beta receptors.

Question 22

What does glucagon do as an inotropic agent

Answer 22

Glucagon stimulates other receptors linked to the same G protein second messengers. Useful if beta-1 receptors are blocked.

Question 23

What does amrinone do as an inotropic agent

Answer 23

Phosphodiesterase inhibitor for heart specific type PDE3, which normally reduces cAMP and so decreases PKA activity, limiting contractility. Inhibiting PDE3 prevents reduction in cAMP, increases PKA activation, more phosphorylation of Ca2+ channels and increased contractility.