15a - Pacemakers and Myocytes Notes

Functions of the heart

1. pump blood: creates BP

2. Endocrine organ: walk of RA secretes atrial natriuretic peptide

What does Atrial natriuretic peptide do?

reduce blood pressure by vasodilating and decreasing blood volume

What are the functions of the valves of the heart?

one way blood flow (via papillary muscles)

slow electrical conduction to allow for proper ventricular filling (AV delay)

What splits the right atrium + right ventricle?

tricuspid valve

What split the left atrium + ventricle?

bicuspid/mitral valve

Blood from the right side of heart goes where

pulmonary circulation

Blood from the left side of heart goes where?

systemic circulation

What are the semilunar valves?

aortic valve

pulmonic valve

What does the aortic valve separate?

aorta and left ventricle

What does the pulmonic valve separate?

the right ventricle from the pulmonary artery

Where are papillary muscles located and what do they do?

part of ventricular wall

connect valve leaflets via chordae tendinae

contract with chamber to prevent valve prolapse and regurgitation

Path of blood through the heart

1. vena cava

2. right atrium

3. tricuspid valve

4. right ventricle

5. pulmonary valve

6. pulmonary arteries

a. arterioles --> capillaries --> venuoles --> veins

7. left atrium

8. bicuspid/mitral valve

9. left ventricle

10. aortic valve

11. aorta

a. systemic arteries --> arterioles --> capillaries --> venules --> veins --> vena cava

What are the layers of the heart from inside out?

endocardium

myocardium

visceral pericardium

pariteal pericardium

What is the endocardium?

vascular endothelium of heart

What is the myocardium? What does it contain?

muscle layer

two cell types connected by gap junctions:

pacemakers

myocytes

What do pacemaker cells do?

set HR

What do cardiac myocytes do?

control strength of contraction

What does the visceral pericardium do?

coronary arteries and veins run here but do not perfuse heart

What is the space between the visceral and parietal pericardium filled with? Why?

filled with pericardial fluid to decrease friction of heart

What are pacemaker cells?

neuron like modified cardiac myocytes

What is chronotropy?

heart rate

What are characteristics of pacemaker cells?

automaticity: brings themselves to threshold by opening + closing Vg channels

sets the contraction rate of mycocytes

fastest pacemaker sets heart rate for entire heart

Which cell exhibits automaticity?

pacemakers

sinoatrial node (SA node) (what is it, what does it do?)

pacemaker cells running from atrium - atrium

sets heart rate

What is the rate of the SA node?

100 bpm, but vagal brake makes it 70bpm

Atrioventrivular (AV) Node (where is it, rate?)

in atrium + septum of ventricle

40bpm (AV-delay)

Bundle of His (where is it, rate?)

in septum wall

15 bpm

Purkinje fibers (where is it, rate?)

base wall of heart + apex

5 bpm

Phases of AP of pacemaker cells

1. Pacemaker potential: cell brought to threshold

a. funny channels open, Na+ influx

b. transient Ca2+ channels open at end, Ca2+ influx

2. Depolarization phase: DHPR/L-type Ca2+ channel opens, Ca2+ influx

3. Repolarization phase: K+ channel opens, K+ efflux

4. No rest, cell immediately begins pacemaker potential

Mechanism of Propagation of AP in heart

1. SA node has AP, causing atrial myocyte depolarization + contraction

2. A-V delay: AP spreads to AV node, AP conduction decreases allowing for ventricular filling

3. AP in bundle of his + purkinje cause depolarization + contraction of ventricles, blood ejects bottom up

Frequency of SA node action potential is equal to?

HR (chronotropy)

What regulates chronotropy? How?

ANS

SNS: B1 receptors, increases chronotropy

PNS: M2 receptors, decrease chronotropy

positive chronotropic agents

Hyperthyroidism (increased T3/T4)

Hyperkalemia

B1 agonist

M2 antagonist

How does increased T3/T4 increase chronotropy?

increases # of B1 receptors

causes faster opening of DHPR

How does hyperkalemia cause increased chronotropy?

smaller K+ gradient, less K+ efflux, cell more depolarized

How does a B1 agonist increase chronotropy?

increase opening of DHPR

negative chronotropic agents

low T3/T4 (hypothyroidism)

hypokalemia

B1 antagonists

M2 agonists

Ca2+ channel blocker

cardiac glycosides

How does low T3/T4 cause decrease in chronotropy

slows opening of DHPR

decreased # B1 receptors

How does hypokalemia cause decrease in chronotropy

larger gradient, more K+ efflux, cell less depolarized

Metoprolol is also called

Lopressor

Metoprolol (Lopressor) what is it

beta 1 blocker

How does Ca2+ channel blockers (non DHPR) decrease chronotropy?

blocks DHPR channels, decreasing Ca2+ (no depolarization)

Exampels of Ca2+ blockers

Phenylalkylamine (Verapamil)

Benzothiazepine (Diltiazem)

Example of Beta 1 blocker

Metoprolol (Lopressor)

How do cardiac glycosides decrease chronotropy?

stimulate vagal nerve, increasing vagal break therefore decreasing heart rate

examples of cardiac glycosides

digoxin

ouabain

Does excitation-coupling of cardiac myocytes have a latent period?

no, therefore can't summate

Excitation (AP) of cardiac myocytes mechanism

1. Depolarization: Na+ channel opens, Na+ influx

2. Slight repolarization:

a. Na+ channel closes

b. transient K+ channel opens

3. Plateau:

a. transient k+ still open

b. DHPR opens, Ca2+ influx

4. Repolarization:

a. DHPR closes

b. inward rectifying K+ channel opens, K+ efflux

5. Rest

Contraction of cardiac myocytes mechanism

1. cell depolarized + brought to threshold by adjacent myocytes AP or by pacemaker

2. AP begins:

a. Na+ channel opens

b. transient K+ opens

c. DHPR opens

3. Ca2+ in cell binds to RyR on SR

4. RyR opens, Ca2+ spark (Ca2+ leaves SR and enters ICF)

5. Ca2+ binds troponin, tropomyosin slides + myosin binds actin, cross bridging + contraction

6. Repolarization via vg K+ channel

How do cardiac myocytes relax?

2 ways:

1. SERCA pumps CA2+ into SR for next contraction

2. Ca2+ is pumped info ECF via secondary active transporter

How does a secondary active transporter pump Ca2+ out of cardiac myocyte?

uses Na+ gradient established by NKA to move Na+ into cell and Ca2+ out of cell

What is inotropy?

force of contraction

What is inotropy based on?

amount of Ca2+ in cell

What regulates inotropy?

SNS (B1)

increase SNS=increase inotropy

decrease SNS= decrease inotropy

positive inotropic agents

B1 agonist

Cardiac glycosides

How does a B1 agonist increase inotropy?

increases DHPR, RyR, SERCA activity

How do cardiac glycosides increase inotropy?

inhibit NKA so secondary transporter cannot remove Ca2+, having Ca2+ enter SR via SERCA

Cardiac glycosides are overall ?

cardiostimulatory

Which effect of cardiac glycosides is stronger ?

increase in inotropy is stronger than its decrease in heart rate

negative inotropic agents

B1 antagonist

CCB

How do B1 antagonist decrease inotropy?

decrease DHPR, RyR, SERCA activity

How does CCB decrease inotropy?

inhibit DHPR

Which CCB is for both cardiac and vascular?

Benzothiazepine (Diltiazem)

What CCB is cardiac specific?

Phenylalkylamine (Verapamil)

Phenylalkylamine other name

Verapamil

Benzothiazepine name brand

Diltiazem

Similarites in cardiac myocyte + skeletal muscle structure

striated

same sarcomere structure

t-tubules

excitation-contraction coupling

How many nuclei per cardiac myocytes?

one, mononucleated cells

intercalated discs

gap junctions connecting cardiac myocytes

How does a CCB affect both HR + strength of contraction?

decreases both

How do cardiac glycoside affect both HR + strength of contraction?

decrease HR

increase strength of contraction

What is the length-tension relationship?

length of a sarcomere before contraction determines strength of contraction

What is the length of a sarcomere in the cardiac myocyte dependent on?

determined by how much blood fills the chambers

another name for length-tension relationship?

preload

venous return

end diastolic volume

frank starling law of heart

if you have a decrease in preload, what happens to tension + strength of contraction?

decreased preload=decrease length of sarcomere=decreased tension = decreased strength

if you have a increase in preload, what happens to tension + strength of contraction?

increase preload=increased length of sarcomere=increased tension = increased strength

How do you increase preload?

venoconstriction (alpha-1, increase SNS)

muscle pump

respiratory pump

How does muscle pump increase preload?

veins between skeletal muscles get pushed on when pumping muscles, pumps blood to heart

How does respiratory pump increase preload?

During inspiration, thoracic pressure drops, drawing blood into heart