6.3 - Cardiac Mechanics

Question 1

What is excitation-contraction coupling?

Answer 1

• excitatory event (AP) at myocyte –> influx of Ca2+ –> Ca2+ release –> contraction
• contraction is very dependent on the influx of external Ca2+ - heart cell will not contract unless this happens
• cardiac APs are longer - important as length of AP dictates strength of contraction

Question 2

What is the length and width of myocytes?

Answer 2

• ventricular cells are 100um long and 15um wide

Question 3

What are T-tubules

Answer 3

• transverse tubules are finger-like invaginations of the cell surface
• spaced so that a T-tubule lies alongside each Z-line of every myofibril
• T-tubule openings are up to 200nm in diameter
• carry surface depolarisation deep into the cell

Question 4

What is the composition of a myocyte?

Answer 4

• 46% myofibrils
• 36% mitochondria - high energy requirement
• 4% sarcoplasmic reticulum
• 2% nucleus
• 12% other

Question 5

How does AP travel from cell surface into cell?

Answer 5

1. AP produced along cell surface
2. depolarisation carried deep into cell down T-tubule and sensed by many L-type Ca2+ channels (LTCCs) in T-tubules
3. alters LTCC conformation and opens it so Ca2+ from outside of cell flows down its concentration gradient into the cytosol
4. this Ca2+ binds to sarcoplasmic reticulum release channels (ligand operated) on SR that then open
5. Ca2+ stored in SR released into cytosol - this Ca2+ binds to troponin in myofilaments and activates contraction
6. to relax, Ca2+ is actively pumped against concentration gradient by SR Ca2+ ATPase into SR where it is ready to be released by next wave of depolarisation
7. the Ca2+ that came into cell to trigger release of Ca2+ is removed from cell during diastolic interval by Na+/Ca2+ exchanger in T-tubule which uses downhill movement energy of Na+ into cell to pump Ca2+ out of cell
8. myocyte now in Ca2+ balance

Question 6

What is the relationship between force production and intracellular Ca2+?

Answer 6

• we can increase Ca2+ in SR with e.g. sympathetic stimulation
• can increase phosphorylation of some proteins and increase Ca2+ influx into cell
• looks like sigmoid curve

Question 7

How does force produced change with muscle length?

Answer 7

• as you increase muscle length and stimulate it, you increase active force production due to cross bridge formation happening in response to Ca2+ being released from SR
• cardiac cells also have some elasticity so have a tendency to recoil as they are stretched - meaning as you increase muscle length, base force produced increases too (called passive force)

Question 8

What is length-tension relation in cardiac vs skeletal muscle?

Answer 8

• initially as length increases, total force increases
• after a certain length, active force and total force decreases in both
• passive force increases as muscle length increases
• total force = active + passive

Question 9

Why does cardiac muscle produce more passive force?

Answer 9

• cardiac muscle is more resistant to stretch and less compliant than skeletal muscle
• due to properties of the ECM and cytoskeleton

Question 10

What does it mean that the cardiac muscle only works on the ascending limb of the length-tension relationship?

Answer 10

• you cannot overstretch cardiac muscle - you can with skeletal muscle (where you pull myofibrils apart)
• heart is contained in pericardial sac so you can only stretch a certain amount

Question 11

What is isometric contraction?

Answer 11

• muscle fibres do not change length but exert force so pressure increases in both ventricles
• when ventricles fill with blood we get isometric contraction and valves are closed so blood does not go anywhere = builds up ventricular pressure
• happens in planks

Question 12

What is isotonic contraction?

Answer 12

• shortening of fibres and blood is ejected from ventricles
• when pressure in ventricles from isometric contraction overcomes backpressure in aorta, blood is expelled from ventricle, ventricular cells shorten and blood is pushed out
• happens in bench press

Question 13

What is preload?

Answer 13

Weight that stretches muscle before it is stimulated to contract

Question 14

What happens to force as preload increases?

Answer 14

As force preload (stretch) increases, force increases up to a point then decreases

Question 15

What can preload be thought of in terms of the heart?

Answer 15

• ventricular filling
• as blood fills heart during diastole, it stretches the resting ventricular walls
• this stretch (filling) determines the preload on the ventricles before ejection
• preload is dependent on venous return
• measures include end-diastolic volume, end-diastolic pressure and right atrial pressure

Question 16

What is afterload?

Answer 16

Weight not apparent to muscle in resting state; only encountered when muscle has started to contract

Question 17

What happens to shortening of muscle as afterload increases?

Answer 17

• as afterload increases, amount of shortening of muscle reduces
• larger the weight, the more difficulty the muscle has to shorten so amount and velocity of shortening decreases
• to change this, change the preload:
• small preload = shorter muscle lengths so less force can be produced
• large preload = longer muscle lengths so more force can be produced

Question 18

What can afterload be thought of in terms of the heart?

Answer 18

• pressure in aorta that ventricle has to overcome once it can generate enough pressure to pump blood out of heart
• afterload is the load against which the left ventricle ejects blood after opening of the aortic valve
• any increase in afterload decreases the amount of isotonic shortening that occurs and decreases the velocity of shortening
• measures of afterload include diastolic blood pressure

Question 19

What is the Frank-Starling relationship (Starling law)?

Answer 19

• as filling of the heart increased, force of ventricular muscle also increased
• law: increased diastolic fibre length increases ventricular contraction
• consequence: ventricles pump greater stroke volume so that, at equilibrium, cardiac output exactly balances the augmented venous return
• if more blood comes into heart, heart filled more, ventricles contract more and vice versa

Question 20

What are two factors that cause the Frank-Starling relationship?

Answer 20

• changes in the number of myofilament cross bridges that interact - as you stretch muscle, you increase number of myofilament cross bridges so more myosin and actin interactions - at shorter lengths than optimal the actin filaments overlap on themselves, reducing number of cross bridges that can be made
• changes in the Ca2+ sensitivity of the myofilaments - precise mechanism unclear but two hypotheses

Question 21

What is hypothesis 1 of mechanism of changes in Ca2+ sensitivity of myofilaments?

Answer 21

• Ca2+ required for myofilament activation
• troponin C is thin filament protein that binds actin and myosin
• troponin C regulates formation of cross-bridges between actin and myosin
• at longer sarcomere lengths, the affinity of troponin C for Ca2+ is increased due to conformational change in protein
• less Ca2+ therefore required for same amount of force

Question 22

What is hypothesis 2 of mechanism of changes in Ca2+ sensitivity of myofilaments?

Answer 22

• with stretch the spacing between myosin and actin filaments (lattice spacing) decreases
• with decreasing myofilament lattice spacing, the probability of forming strong binding cross-bridges increases
• this produces more force for the same amount of activating Ca2+

Question 23

What is stroke work?

Answer 23

• work done by heart to eject blood under pressure into aorta and pulmonary artery
• stroke work = volume of blood ejected during each stroke (SV) x pressure at which blood is ejected (P)
• stroke work = SV x P
• preload and afterload greatly influence SV
• cardiac structure greatly affects P

Question 24

What is the law of LaPlace?

Answer 24

• when the pressure within a cylinder is held constant, the tension on its walls increases with increasing radius
• wall tension = pressure in vessel x radius of vessel
• T = P x R
• incorporating wall thickness (h) amends this to:
• T = (P x R)/h
• in the heart, the RV and LV have blood of different pressure but we want tension to remain the same = we can have them have different radii