PSIO 429 Cardiac Muscle

Contraction Steps (Ca⁺ pathway)

1. Action potential gets to t-tubule

2. opens LTCC

3. Ca enters

4. Opens RyR on SR

5. Ca leaves SR

6. Ca bind to TnC to turn on contraction

to relax..

SERCA pump Ca back into SR on every beat

contracted muscle gets decrease [Ca] AND replenish SR before next AP

Chemomechanical Cycle

1. Post-Rigor - ATP bound

2. ATP hydrolysis

3. Pre-Power Stroke phase - cock back

4. Pi release, power stroke happens

5. ADP dissociates - Rigor

6. New ATP binds, back to post rigor

Cross Bridge Cycle

1. ATP hydrolysis, cocking

2. Ca bind to TnC, stop TnI from inhibiting Tm binding

3. Myosin binds to actin

4. Pi release, power stroke

5. ADP release, rigor

6. new ATP bind

7. release actin filaments

TnC

only 1 Ca binding site

less activation of contraction (slower, less force)

tropomyosin

decreases mysoin ATPase activity

Troponin Genes

cTnC - TNNC1

cTnI - TNNC3

cTnT - TNNT2

cTnI

extra tail N-terminus

helps change cardiac output

phosphorylation site for PKA - Ca comes off faster, faster relaxation

cTnT

extra N-terminus

stronger bind to Tm than skel

flow of electricity in heart

SA Node - AV node - His bundle - Right and Left ventricular bundles - Purkinje fibers

EKG phases (order of letters)

P wave, PR segment, QRS complex, ST segment, T wave

EKG phases (what happens in heart)

pacemakers leak to threshold

P Wave: atrial depol

PR/PQ seg: atrial contraction and AV pause to slow potential

QRS complex: atrial repol, ventricular depol

RT segment: vent. contract

T wave: vent repol

T wave vs P wave

T wave is bigger because vent. is bigger than atria

AV pause

slows the potential to give the atria time to contract

pacemaker rates (SA, AV, His, Purkinje

SA - 100-110/min

AV - 40/min - can support life w/o SA

His - 20-40/min

Purkinje - 20-40/min

Pacemaker Action Potential (steps only)

4. Pacemaker Potential

0. Depol

3. Repol

   1. PSlow depol (pacemaker potential)

Pacemaker Potential (ions causing)

4. Pacemaker potential - Na IN through Na sensitive channels - funny

0. Depol - Ca in through gated channels at threshold

3. Repol - K leave through sensitive channel, not funny

4. slow repol/pacemaker potential - Na in through funny, K out through funny

Ventricle Action Potential (steps only)

0. depolarization

1. slight repol

2. plateau

3. late repol

4. resting at -90

Ventricle AP (ions causing)

0. depol - Na in through gated channels

1. early repol - Na close, K open, out

2. plateau - K out and Ca in

3. late repol - Ca close, K still out, open until resting

4. resting at -90mV by Na/KATPase

ANS effect on rate

PNS - decrease rate, more active at rest, inhibits SA node

SNS - increase rate

SNS changes to SA node potential

1. faster repol (more K out)

2. faster depol (more Ca in)

3. repol less

4. pacemaker depol is faster (higher funny channel current)

PNS effects on SA node AP

1. slower repol (less K)

2. slower repol (less Ca)

3. repol more

4. slow pacemaker potential (less funny current)

T-Tubules in different cell types

high in myocyte

low in pacemakersR

RyR in different cell types

spread out in both

striated because it localizes by actin

closer Ca handling to actin helps function

modulate force (3 ways)

inotropy - ions come in, makes more forceful

chronotropy - time, beats more quickly

lusitropy - relax easier

beta-adrenergic receptor pathway

NE bind to GPCR beta1

alpha-S activate adenylyl cyclase

AC turns ATP to cAMP

cAMP activates PKA

PKA phos. proteins

proteins that PKA phosphorylates (7)

1. LTCC

2. phospholamban (PLN)

3. RyR

4. cMyBP-C

5. cTnI

6. Titin

7. HCN4 (funny)

LTCC phos.

more LTCC activation → + chronotropy → beats faster

more Ca influx → + inotropy → beats forcefully

PLN phos.

more SERCA activation → + chronotropy, +inotropy → faster, forceful

higher Ca uptake rate → + lusitropy → relax quickly

RyR phos.

increase rate of SR Ca release → +inotropy → more forceful

cMyBP-C phos.

more myosin activation → + inotropy → more forceful

higher rate of cross bridge detach → lusitropy → relax quicker

phos. on different sites does different things

activates heart

cTnI phos.

higher rate of Ca dissociation from TnC → lusitropy, chronotropy → relaxes quickly

Titin phos.

more titin compliance (less springy) → +lusitropy → relaxes quickly

less myocyte stiffness

HCN4 phos.

more sensitive to hyperpolarization, increase in current → chronotropy → channels are quicker to open, more current, beats faster

HCN$ stands for…

Hyperpolarization Activated Cyclic Nucleotide Gated Channels

cMyBP-C attaches where?

Nterm in actin or myosin (flippable)

Cterm in myosin

in ZoO and were heads are in H zone

phospholamban

inhibits SERCA

stops when phos.

more relaxation

more PLN phos, more force on next beat

Muscarinic Signaling Pathway

ACh to GPCR - M2

gamma and beta to rectifying K channel

alpha-i inhibit adenylyl cyclase

less ATP → cAMP

less PKA activation

less phos.m

muscarinic results in

lower heart beat and contractility

- lusitropy, inotropy, chronotropy

PNS

adrenergic results in

SNS

higher heart rate and contractility

postitive lusitropy, chronotropy, inotropy

Baro Reflex - cardioacceleratory center

SNS

inhibited by stretch in carotid artery

Baro Reflex - cardioinhibitory center

PNS

activated by stretch in carotid artery

Baro Reflex - vasomotor center

inhibited by stretch in carotid

stiffens vessels

Baro Reflex - sitting down

higher BP → more stretch → AP from cranial nerve to brain stem → inhibit cardioacceleratory and vasomotor, stim. cardioinhibitory → more PNS, less SNS → lower heart rate and contractility → BP lowers back to normal

Baro Reflex - standing up

lower BP → less stretch → less AP → less inhibition of cardioacceleratory and vasomotor, less stim. of cardioinhibitory → higher heart rate and contractility → BP goes back up to normal

cranial nerve in Baro

glossopharyngeal - from carotid to brain stem

vagus - from aortic to brain stem

baro reflex efferents

PNS - vagus

SNS - to heart and vasculature

length-tension relationship

looks like skeletal

no plateau

starts to go up at 90%, peak at 110%, linear down to 190%

cardio output

how much blood pumped in amount of time

stroke volume x heart rate

stroke volume

volume of blood per beat

blood flow through heart

1. Right atria

2. tricuspid valve to R vent.

3. pulmonary valve to Pulmonary trunk

PULMONARY CIRCUT

4. splits into pulmonary arteries

5. lungs, get oxygenated

6. pulmonary veins

7. L atrium

8. bicuspid valve to L vent.

9. aortic valve to aorta

SYSTEMIC CIRCUT

10. arteries to systemic use

11. exchange O2 at cap. beds

12. veins

13. vena cava

14. R atrium