BPK 305 - Lecture 2

What is systemic circulation?

Oxygenated arterial blood in multiple parallel paths

What is pulmonary circulation?

De-oxygenated arterial blood

Why is systemic circulation in parallel and not series?

Oxygen distribution would be unequal

Lower resistance

Deliver blood where it's most needed

What does the annulus fibrosis do?

- provides structural integrity

- electrical isolation

What does electrical isolation do?

Allows different patterns of APs in atria and ventricles

What do the papillary muscles do?

Pull on the christening tendinae to stop back flow in the heart

What is the ventricular wall made up of?

Endocardium

Myocardium

Epicardium

Endocardium composition

simple squamous epithelium

Myocardium composition

95% cardiomyocytes

Epicardium composition

Squamous epithelium, vessels, nerves, minimal fat

Adult cardiomyocyte size

120-150um long

10-20 um wide

Rectangle

When does cardiomyocyte size change?

Pressure overload

Volume overload

What does pressure overload cause?

increased cell width 2-3 fold

more parallel contractile units

What does volume overload do?

Increased cell length up to 10-20%

Stretching contractile units

When does pressure overload occur?

hypertension and weight lifting

When does volume overload occur?

Valve failure and aerobic exercise

Z line

- forms sarcomere boundary

- thin actin filaments run through

- contains alpha actin

I band

- decreases with contraction

- increases with relaxation

- contains actin

A band

- contains myosin

- does not change with contraction

H band

- center of A band

- no overlapping actin

M line

Attachment for myosin

Resting sarcomere length

2.2 um

Cardiomyocyte structural elements

- contractile

- T-tubules

- mitochondria

- SR

- nucleus

- golgi

- ribosomes

How much of the cell does contractile elements make up?

50%

What do t-tubules align with?

Z lines

How much of the cell is mitochondria?

30-35%

Types of mitochondria

Subsarcolemma

Intermyofibrillar

subsarcolemmal mitochondria

located below sarcolemma

Intermyofibrillar mitochondria

located around contractile proteins

What does myocyte branching do?

Provides longitudinal and diagonal coupling

What are macula adherens?

Cytoskeleton proteins for physical coupling

What are gap junctions?

Connexins for electrical coupling

What do gap junctions create?

Functional syncytium

What are gap junctions made of?

2 connexons

What makes a connexon?

Hexamers, 6 connexins

What do gap junctions do?

Regulate permeability

Where is titan found?

M line to Z line

What is titan?

Largest known protein

What does titan do?

Acts like a spring

Stabilizes position of contractile elements

Returns muscle to resting length

Where is nebulin found?

From Z line to thin filament ends

What does nebulin do?

aligns actin

Regulates thin filament length

Actin filament structure

Helical, 13 molecules per turn

Tropomyosin structure

Lies near actin groove

2 per actin turn

What is in the troponin complex?

- TnT tropomyosin binding

- TnC Ca binding

- TnI inhibitory

Cross bridge cycling steps

1. Myosin is stuck to actin

2. ATP binds to myosin head causing the dissociation of the actin-myosin complex

3. ATP is hydrolyzed causing myosin heads to return to resting state

4. A cross bridge forms and myosin head binds to a new position of actin

5. P is released, myosin heads change conformation resulting in the power stroke

6. ADP is released

What does cross bridge cycling strength depend on?

Number of cross bridges

What does the speed of cross bridge cycling depend on?

Rate of ATP hydrolization

How is contraction regulated?

Calcium concentration

What are the four binding sites of troponin?

Site I-IV

Troponin site I

Dysfunctional

Troponin site II

Initiates contraction

Troponin sites III and IV

high affinity, always occupied

What does Ca binding to TnC do?

Initiates contraction

Where is tropomyosin located?

Near actin groove

What does tropomyosin do?

Interferes with myosin binding

What does TnT bind to?

tropomyosin

What does TnC bind to?

Calcium

What does TnI bind to?

actin

What are the steps for XB cycling initiation?

1. Increased Ca

2. Ca binds to TnC at site 2

3. TnI and tropomyosin move into the grove

4. XB cycle

5. Contraction

Heavy myosin chains

- 2 chains form a coiled helix

- tail and 2 heads

Myosin head binding sites

1 for ATP and 1 for actin

Myosin light chain

2 pairs

Regulatory or phosphorylatable

Essential or alkali

What are the heavy chain isoforms?

Alpha and beta

What do different isoforms of myosin heavy chains do?

Different rates of ATP breakdown

Different rates of contraction

How can heavy chain isoforms change?

Thyroxine increases alpha

What heavy chain isoforms is the fastest?

Alpha