ICL 1.9: Principles of Cardiac Physiology

Question 1

how are cardiac muscle cells connected?

Answer 1

intercalated disks

they help with transmission and tensile strength

Question 2

what are the structural parts of a sarcomere?

Answer 2

1. myosin = thick filament
2. actin = thin filament

has tropomyosin and troponin on it

actin is connected to actinin

slide 5

Question 3

what is one of the most common causes of hypertrophic cardiomyopathy?

Answer 3

abnormality of the beta myosin heavy chain genes!

aka something wrong with the sarcomere unit!

Question 4

what is the z band?

Answer 4

actinin attaches to the actin

it’s the line separating one sarcomere from another

Question 5

what is the I band?

Answer 5

regions composed only of actin filaments

Question 6

what is the A band?

Answer 6

the portion of the sarcomere containing myosin, which overlaps with actin except in the central H zone

the A band does not change size during contraction

Question 7

what is the H band?

Answer 7

a central segment within the A band of a myosin filament

contains only myosin filaments

decreases in size during contraction

Question 8

how does a sarcomere contraction work?

Answer 8

tropomyosin is coiled around the actin filament

the troponin complex binds tropomyosin to form a complex with all 3 of them

troponin C will bind Ca+2 which will allow for ATP to bind and allow for a power stroke and the myosin head attaches to the actin and power strokes

in the absence of Ca+2, troponin-I (inhibitory) and tropomyosin prevent actin-myosin cross-bridging

when Ca+2 increases, troponin-I undergoes a confrontational change and rotates tropomyosin out of the way so that myosin can bind to actin

Question 9

what happens to the troponin complex during an MI?

Answer 9

during a myocardial infarction, cardiac troponins are released into the circulation

cardiac and skeletal muscle TnC are identical, but cardiac and skeletal muscle TnI & TnT have different amino acid sequences so they can be differentiated

detection of cardiac TnI and TnT in the circulation suggests myocardial damage

sometimes it takes a couple hours for the troponin levels to rise (3 hrs) so if you walk into the ED 1 hr after an MI they will trend troponin to see where it’ll be at 3 hours out –> will be elevated up to 7 days later

Question 10

what is the Rigor complex?

Answer 10

1. ATP binds to myosin head causing the dissociation of the actin-myosin complex
2. ATP is hydrolyzed to ADP causing myosin heads to return to their resting conformation
3. a cross-bridge forms and the myosin headbands to a new position on actin
4. phosphate is released. myosin heads change conformation, resulting in the power stroke. the filaments slide past each other
5. ADP is released

Question 11

what is the sliding filament mechanism?

Answer 11

1. increase in calcium starts filament sliding by binding TnC and tropomyosin will get moved away so myosin can bind actin
2. decrease in calcium turns off sliding process
3. thin filaments on each side of sarcomere slide inward over stationary thick filaments towards A band during contraction
4. as thin filaments slide inward, z-line is pulled inward
5. sarcomere shortens

Question 12

how does calcium homeostasis in cardiac myocyte?

Answer 12

the sarcoplasmic reticulum is where the majority of your calcium is stored in the myocyte

to release Ca+2, there are ryanodine receptors that bind Ca+2 and allow for Ca+2 release from the SR

together, intracellular and extracellular calcium initiate cardiac contraction

Question 13

what’s the difference between action potential and muscle contraction?

Answer 13

the actual muscle contraction of the heart will lag a little behind the action potential

Na+2 is firing the action potential just like every other cell and then you get Ca+2 homeostasis and eventually closing of Ca+2 channels that allow Ca+2 to stay intracytosolically till it can cause a contraction

K+ will repolarize the action potential when the contraction has happened

Question 14

what causes QT elongation?

Answer 14

when you have problems with the action potential, you can get a QT elongation from a Na+ or K+ channel problem

Question 15

once calcium has been released from the sarcoplasmic reticulum, how do you get it back in?

Answer 15

calcium removal during diastole is an active process aka you need ATP!

phospholambans help pump Ca+2 back into the SR

this allows cardiac muscles to relax by preventing actin-myosin cross bridging

Question 16

what’s the long winded way of explaining a cardiac contraction?

Answer 16

the process by which the action potential of the cardiac myocyte leads to contraction is termed excitation-contraction coupling

cardiac muscle is excited and the excitation spreads into the interior of the cells via the T tubules, which invaginate the cardiac fibers at the Z lines

during the plateau (phase 2) of the action potential, permeability of the sarcolemma to Ca++ increases. Ca++ flows down its electrochemical gradient and enters the cell through Ca++ channels (L-type) in the sarcolemma and in the T tubules

however, the amount of Ca++ that enters the cell interior from the extracellular/interstitial fluid is not sufficient to induce contraction of the myofibrils – instead, it acts as a trigger to release Ca++ from the SR

Ca++ leaves the SR through Ca++ release channels, which are called ryanodine receptors because the channel protein binds ryanodine avidly –> cytoplasmic [Ca++] increases from a resting level of about 10−7 M to levels of about 10−5 M during excitation –> this Ca++ then binds to the protein troponin C

the Ca++-troponin complex interacts with tropomyosin to unblock active sites between the actin and myosin filaments – this unblocking initiates cross-bridge cycling and hence contraction of the myofibrils

mechanisms that raise cytosolic [Ca++] increase the force developed, and those that lower cytosolic [Ca++] decrease the force developed cardiac diastole is initiated when the inflow of Ca++ stops and the ryanodine receptors close; this starts at the terminal part of the phase 3 of the action potential

now the SR avidly takes up Ca++ by means of a Ca++-ATPase – thus, cardiac diastole is also an active process and peaks during the phase of 4 the cardiac action potential

phase 4 of the action potential is shortened during peak heart rates; this provide little opportunity for the heart to fully relax thus, reducing cardiac compliance and filling

Question 17

what is the MOA of digoxin?

Answer 17

by inhibiting the Na/K pump you maintain Ca+2 intracellularly for a longer period of time which increases contractility

Question 18

how does sympathetic stimulation affect cardiac contraction?

Answer 18

1. SNS activation increases intracellular calcium via opening of the L-type Ca++ channels that, in turn, releases more Ca++ from the SR
2. phosphorylation of phospholambin increases Ca++ uptake and stimulates relaxation (lusitropy)
3. PKA-dependent troponin I phosphorylation reduces myofilament sensitivity for Ca, which is intrinsically negatively inotropic, but has the benefit of faster dissociation of Ca2+ from myofilaments, which hastens relaxation and diastolic filling

Question 19

what are passive and active tension?

Answer 19

passive tension is elastic recoil of the muscle

active tension is active squeezing of the heart

they’re really important because they help explain the Frank-Starling law –> by increasing preload you increase passive tension because you’re stretching something out that naturally wants to go back to its original conformation so by giving preload in someone with normal squeeze, you increase your ventricular function and increase your active tension!

Question 20

what is the function of titin? what can happen if titin isn’t working?

Answer 20

it helps prevent dilated cardiomyopathy!

it protects the sarcomere from stretching out farther than it should to the point that myosin-actin bridging can’t happen

if you can’t squeeze your heart because it’s so dilated and you can’t get blood out you’ll build up back pressure in the pulmonary veins which causes pulmonary edema and hypoxia

Question 21

what is the law of Laplace?

Answer 21

T = P x R

the heart performs work in generating tension, not pressure – so the greater the tension, the greater the cardiac work

ventricular dilation like in dilated cardiomyopathy or CHF leads to increased wall tension even if the pressure in the ventricular cavity is near normal which adversely affects coronary supply and increases cardiac work!! which is bad because you already have a diseased heart you don’t want to increase work!!

so you give diuretics to heart failure patients because you don’t want to stretch your heart out even more because they can’t accommodate preload – also if you have coronary artery disease with left CHF and you have systolic dysfunction that builds up pressure in the lungs and can cause pulmonary edema