ICL 1.9: Principles of Cardiac Physiology Flashcards
how are cardiac muscle cells connected?
intercalated disks
they help with transmission and tensile strength
what are the structural parts of a sarcomere?
- myosin = thick filament
- actin = thin filament
has tropomyosin and troponin on it
actin is connected to actinin
slide 5
what is one of the most common causes of hypertrophic cardiomyopathy?
abnormality of the beta myosin heavy chain genes!
aka something wrong with the sarcomere unit!
what is the z band?
actinin attaches to the actin
it’s the line separating one sarcomere from another
what is the I band?
regions composed only of actin filaments
what is the A band?
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
what is the H band?
a central segment within the A band of a myosin filament
contains only myosin filaments
decreases in size during contraction
how does a sarcomere contraction work?
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
what happens to the troponin complex during an MI?
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
what is the Rigor complex?
- ATP binds to myosin head causing the dissociation of the actin-myosin complex
- ATP is hydrolyzed to ADP causing myosin heads to return to their resting conformation
- a cross-bridge forms and the myosin headbands to a new position on actin
- phosphate is released. myosin heads change conformation, resulting in the power stroke. the filaments slide past each other
- ADP is released
what is the sliding filament mechanism?
- increase in calcium starts filament sliding by binding TnC and tropomyosin will get moved away so myosin can bind actin
- decrease in calcium turns off sliding process
- thin filaments on each side of sarcomere slide inward over stationary thick filaments towards A band during contraction
- as thin filaments slide inward, z-line is pulled inward
- sarcomere shortens
how does calcium homeostasis in cardiac myocyte?
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
what’s the difference between action potential and muscle contraction?
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
what causes QT elongation?
when you have problems with the action potential, you can get a QT elongation from a Na+ or K+ channel problem
once calcium has been released from the sarcoplasmic reticulum, how do you get it back in?
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
what’s the long winded way of explaining a cardiac contraction?
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
what is the MOA of digoxin?
by inhibiting the Na/K pump you maintain Ca+2 intracellularly for a longer period of time which increases contractility
how does sympathetic stimulation affect cardiac contraction?
- SNS activation increases intracellular calcium via opening of the L-type Ca++ channels that, in turn, releases more Ca++ from the SR
- phosphorylation of phospholambin increases Ca++ uptake and stimulates relaxation (lusitropy)
- 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
what are passive and active tension?
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!
what is the function of titin? what can happen if titin isn’t working?
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
what is the law of Laplace?
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
