Why is the orientation of the ventricle muscle fibers of the heart different?
Diagonally, gives the heart a "wringing" motion to squeeze blood into the aorta or pulmonary trunk
What are desmosomes and what are they made of?
Cell-cell junctions, anchor myocardiac cells together
Made of cadherins
What are gap junctions and what are they made of?
Create channels between cells for ion flow
What ions flow through gap junctions?
Na+ and Ca2+ to trigger depolarization in neighboring cells
Detail the 3 types of myocytes:
Action potential shapes?
Normal cardiac curve
Bundle of His
Detail each ion during the cardiac myocyte action potential (atria/ventricle lineage)
What channels are involved in Phase 0?
Voltage-gated Na+ channels
Fast depolarization, spreads along sarcolemma and T tubules
What channels are involved in Phase 2?
L-type voltage gated Ca2+ channels
Helps create plateau phase, delaying repolarization and allowing calcium entry into cells, which triggers calcium-induced calcium release from SR, which is critical for cardiac muscle contraction
What channels open at phase 2 and 3?
Voltage gated K+ channels
Promote repolarization, open transiently at phase 1
What do Na++ leak channels do?
Slight diffusion of Na+ into cell in phase 4, influences resting membrane potential a bit by making it slightly less negative
What do K+ leak channels do?
Diffusion of K+ out of cells, creates negative resting membrane potential during phase 4, helps in repolarization of excitable cells
What are Na+/K+ ATPase pumps for?
Act to maintain concentration gradients of K+ inside cell and Na+ outside cell. Requires ATP.
If pump activity is decreased, Na+ builds up inside cell.
Can affect other transporters like Na/Ca exchanger or Na/H exchanger
Phase 3 and 4
Detail order of depolarization in heart, with timing as well
SA node: 20 ms
Atrial muscle: 20 ms
AV node: 60 ms
Ventricular muscle: 150 ms
Detail ion movement in ventricular myocytes
Detail ion movement in pacemaker cells
What happens in the cardiac myocyte after Ca2+ and Na+ flow in through gap junctions?
Triggers voltage-gated Na+ channels in the sarcolemma and T-tubules, and the depolarization is able to trigger calcium release from the SR and contraction of the myocyte
Can summation and tetany occur in cardiac muscle cells?
NO (unless pathologicaly)
Rhythm and contractions are cyclical with contractiona dn relaxation, allowing for effective pumping by the
Compare refractory periods between skeletal and cardiac muscle
Skeletal: 5 ms
Cardiac: 200 ms
Detail absolute and relative refractory period in a cardiac cell
In the absolute refractory period, no stimulus from neighboring cells can activate the cell. All Na+ channels are inactivated
Towards the middle/end of Phase 3, some Na+ channels are reset and a relative refractory period results.
Drugs that target various ion channels can alter the duration of the action potential, and thus change the length of the refractory period only!
What is long QT syndrome?
Some drugs, electrolyte imbalance, and genetic conditions alter the function of voltage-gated K+ channels in the heart, which can delay/prolong repolarization
Can cause dangerous/fatal arrhythmias
K+ channels have a repolarization delay
How does hyperkalemia affect cardiac cella ction potential?
Shortens it and lowers the threshold
How does hypokalemia affect cardiac cell action potential?
Lengthens it and increases the threshold
Depolarization of neighboring cells leads to Na+ and Ca2+ entry through _____
This activates voltage-gated ___ channels in the sarcolemma and T tubules
This triggers voltage-gated ____ Ca2+ channels in the T tubules to open
Calcium entry then causes calcium-induced calcium release from ____ receptor ____ channels in the SR to open
Calcium levels increase inside the cell and bind to _____
____ then rotates and myosin heads are able to bind to ____ of the thin filaments
What are the 3 types of troponin and what do they bind?
Troponin C : calcium ions
Troponin T : tropomyosin
Troponin I : actin
What can you test for in lab values?
Troponin I levels
What gene is for voltage-gated L type calcium channels in the heart?
Variant A: ventricle
Variant B: smooth muscle (DHP binds these best)
How does the heart reduce intracellular Ca2+ to allow muscle relaxation?
1) SERCA pumps
2) Na/Ca exchangers
How does the Na/Ca exchanger work?
Normally uses the movement of Na+ into the cell in order to transport calcum out of the cell during relaxation of contractile myocytes.
What happens if Na+ concentrations rise inside the cell?
This transport reduces activity leaving Ca2+ inside the cell...it can reverse its transport too and move more Ca2+ inside
How does the Na/H exchanger work?
Uses the movement of Na+ ions into the cell in order to transport H+ ions out of the cell. Loss of the Na+ gradient can lead to H+ extrusion from the cell, and acidification of the inside of the cell
What is ATP needed in the cardiac myocyte for?
How does low oxygen in the myocyte cause chest pain?
Angina pectoris often results from ischemic episodes that excite chemosensitive and mechanoreceptive receptors in the heart. Ischemic episodes release a collage of chemicals, including adenosine and bradykinin, that excites the receptors of the sympathetic and vagal afferent pathways. Sympathetic afferent fibers from the heart enter the upper thoracic spinal cord and synapse on cells of origin of ascending pathways. Excitation of spinothalamic tract cells in the upper thoracic and lower cervical segments, except C7 and C8 segments, contributes to the anginal pain experienced in the chest and arm. Cardiac vagal afferent fibers synapse in the nucleus tractus solitarius of the medulla and then descend to excite upper cervical spinothalamic tract cells. This innervation contributes to the anginal pain experienced in the neck and jaw. The spinothalamic tract projects to the medial and lateral thalamus and, based on positron emission tomography studies, activates several cortical areas, including the anterior cingulate gyrus (BA 24 and 25), the lateral basal frontal cortex, and the mesiofrontal cortex.
What are the two ways that the heart myocytes can increase strength of contraction?
1) Stretching the myocytes (sarcomere length)
2) Increasing contractility (involves Ca2+)
What is the Frank-Starling Law of the Heart?
If you fill the heart more --> stretch heart muscle (increasing myocyte length) --> greater force production during impending contraction
Fill heart more = pump more!
Also called the length-tension relationship
How does the "palpation" translate to patients?
When the heart "pauses" after a premature beat, it allows greater time to fill which stretches the heart more. This more forceful contraction can sometimes be felt consciously by patients as a palpation or a "skipped beat"
How does Ca2+ concentration cause more contractility?
More calcium = more cross-bridges = more force
How do you increase calcium entry?
Through L type Ca2+ channels
How do you increase calcium release?
SR (ryanodine receptors)
How do you increase calcium sensitivity of the heart?
What is ionotropy?
Any agent that causes more muscular contraction
What is dromotropy?
AV node influence
What is chronotropy?
SA node influence
What part of the nervous system regulates L-type Ca2+ channels?
Detail the steps sympathetic neurons take to cause more force of contraction
Norepi binds to B1 adrenergic receptors, increases cAMP, activates L-type Ca2+ channels, calcium levels increase during contraction
Atrial/ventricular myocytes are mostly innervated by what system?
Pacemaker cells are innervated by what?
Both divisions of ANS
How does paraNS work on pacemaker cells?
ACh acts via M2 receptors to REDUCE heart rate
How does sympNS work on pacemaker cells?
Acts via B1 adrenergic receptors to increase heart rate
Mediated by cAMP acting on ion channels that alter pacemaker action potentials