CARDIAC UNIT: CARDIAC CONTRACTILE ELEMENTS Flashcards
Differentiate between the different circulator system types
systemic: oxygenated arterial blood with multiple parallel paths to supply tissue
Pulmonary: deoxygenated arterial blood
define: mitral valave
located between the upper left heart chamber (left atrium) and the lower left heart chamber (left ventricle)
define and describe the: tricuspid valave
controls the flow of blood from your heart’s right atrium (top chamber) to the right ventricle (bottom chamber
- greater stability for the higher pressure the right side of the heart sees
describe the function of the annulus fibrosus
supports valves preventing prolapse. provides electrical insulation between atria and ventricle
Describe the structure of the ventricles
Left ventricle is thicker - pumps blood to systemic circulation
Right ventricle is 5x lower in blood pressure
Give the function of the chordae tendinae
Chordae tendinae - regulate and support valves (provide tension)
differentiate between the endocarium, myocardium, and epicardium
- Endocardium: inner lining of the ventricular wall
- Myocardium: middle layer of ventricular wall - made up of 95% cardiomyocyte by mass
- Epicardium: outer layer of the ventricular wall
Describe the cellular ultrastructure of the cardiac myocyte
Striated muscle
120-150 μm long
10-20 μm wide
Rectangular shape
In comparison to a skeletal muscle cells, cardiomyocytes are much smaller
What are the physiological adaptions that occur when there is pressure overload in the heart
Can be due to hypertension, weightlifting
High pressure means the heart works harder
- Causes: increased myocyte width 2-3 fold (build more contractile elements to handle load)
- More parallel contractile units
How can volume overload in the heart occur? What are the physiological adaptations when there is volume overload in the heart
- Can be due to valve failure or aerobic exercise
- Valve failure can cause backflow
- Valve failure incident increases with age
- Causes: increased cell length up to 10-20% due to the stretching of contractile units
Describe sarcomere structure
~2.2 um
Made up of thin actin and thick myosin filaments
Define: sarcomere
basic contractile unit of a muscle fiber
Define: Z line
any of the dark thin bands across a striated muscle fiber that mark the junction of actin filaments in adjacent sarcomeres
forms sarcomere boundary
thin filaments run through the Z line
contains α-actinin
~2.2 μm long
Define: I band
The region of a striated muscle fibre that contains only thin (actin) filaments
decreases with contraction
increases with relaxation
contains only actin filaments
Define: A band
The dark band of the muscle sarcomere that corresponds to the thick myosin (protein) filaments
contains thick myosin filaments
doesn’t change with contraction
Define: H zone/band
the central zone of a sarcomere that looks lighter under a microscope. This area of the sarcomere is a lighter portion of the A-band where there is no overlap between the thinner filaments (actin), and the thicker filaments (myosin).
centre of A band (myosin)
Define: M line
thin dark line across the center of the H zone of a striated muscle fiber
attachment for myosin
List and describe the 7 structural elements of the cardiomyocyte cell.
- Contractile elements (sarcomeres) make up 50% of cell volume
Other 50%:
- T-tubules: invagination of the sarcolemma at Z line
- Bring iron right into heart of muscle
- align with Z-lines
3.Mitochondria: energy generation
make up 30-35% cell volume
- Subsarcolemmal mitochondria: to provide energy for ATP driven transport like ATP driven pumps (potassium, calcium, etc.)
- Intermyofibrillar mitochondria: to provide energy for cross bridge cycling
- Sarcoplasmic reticulum: repository for Ca2+ - modified form the endoplasmic reticulum
- Nuclei
- mono or binucleated
-In skeletal cells, they’re polynucleated - Golgi
- Ribosomes
Explain how cardiac myocytes are physically and functionally coupled
- Myocyte branching: myocytes are connected. they are coupled at intercalated disks. allows heart muscle fibers to contract in unison
- provides longitudinal and diagonal coupling - Macula adherens (aka desmosomes):
- cytoskeletal proteins provide physical coupling (“stitches”) between cells - Gap junction (aka nexus): allows muscle fibers to be connected electrically. Connexins provide electrical coupling which creates a functional syncytium
- there are 2 connexons per gap junction.
- a connexon is a hexamer of 6 connexins
- regulated by permeability (e.g. by acidosis)
Define: functional syncytium
Functional syncytium: a unit of contraction comprised of a network of electrically and physically connected cardiac muscle cells (via gap junctions and desmosomes)
able to contract without CNS input
What is the ratio of actin to myosin?
2-1
Define and describe titin
Titin: largest known protein. Exists from M-line to Z-line (half a sarcomere long). Stabilizes position of contractile elements. Acting like a spring, returns stretched muscle to resting length. Protects the heart from being stretched too much.
Define and describe nebulin
- from Z line to thin filament ends
- Runs along thin filament and stabilizes structure
How do thin filaments form? Describe structure of thin filaments.
G-actin twists self to become actin filaments.
Helical in shape. 13 molecules per turn
Describe two 2 important proteins on actin
tropomyosin: lies near actin groove and interferes with myosin binding. Regulates muscle contraction and relaxation
troponin (Tn) complex: Ca2+ regulator important in muscle contraction
- TnT - tropomyosin binding
- TnC - Ca2+ binding
- TnI - inhibitory
Describe 1 cycle of cross-bridge cycling
- ATP binds to myosin head, causing the dissociation of the actin-myosin complex
- ATP is hydrolyzed, causing myosin heads to return to their resting conformation
- A cross-bridge forms and the myosin head binds to the new position of actin
- Phosphate is released. Myosin heads change conformation, resulting in the power stroke. The filaments slide past each other
- ADP is released
Discuss the role of calcium in cardiac muscle contraction
Contraction is regulated by intracellular concentration of Ca2+. When Ca2+ concentration increases, % maximum force exerted by muscle (basically how contracted the muscle is), increases. It is a sigmoidal relationship.
Discuss and describe the importance of:
- diastaloic level of calcium
- systolic level of calcium
- 10 micromolar of calcium
- 100nM diastolic (resting) level of calcium produces very little tension and contraction
- 1 micromolar - systolic level of calcium - half maximum force generated. We rarely ever go above this, even when exercising hard.
10 micromolar - maximum contraction at the muscle
Describe the importance of troponin C (from the troponin complex) in cardiac muscle contraction. Describe all 4 of its Ca2+ sites.
Has 4 sites for Ca2+ to bind to. The binding of Ca2+ to TnC initiates contraction
Site I: dysfunctional in cardiac muscle - in skeletal muscle involved in contraction regulation
Site II: binds to Ca2+ and regulates contraction (sole site of regulation in cardiac myocytes). in skeletal muscle involved in contraction regulation
Site III and IV: high affinity for calcium and always occupied (even at diastolic level of calcium)
Describe what the different components of the troponin (Tn) complex bind to
TnT binds tropomyosin
TnC binds calcium (this is what initiates contraction)
TnI binds actin
What happens when Ca2+ concentration increases in muscle?
- Ca2+ binds to to TnC’s second site, initiating contraction
- Reorgnaization of troponin and tropomyosin: TnI binds to actin, TnT binds to tropomyosin. Both the TnI and tropomyosin moves and expose the myosin binding site on actin
- Cross bridge cycling occurs leading to ….
- Contraction!
What 2 type of chains make up thick filaments?
Heavy chains and light chains
Describe in detail the structure of thick filaments’ heavy chains
Thick filaments are made up of heavy chains and light chains
Heavy chains are two chains that form a coiled helix. Has 2 heads and a tail. Heads are sometimes called S1. Heads have binding sites for actin and ATP which are important for cross bridge cycling.
Heavy chains have alpha or beta isoforms. Each isoform has different rates of ATP breakdown and different rates of contraction.
Different configurations of alpha and beta isoforms
a-a= V1 (fastest)
a-b= V2 (second fastest)
b-b= V3 (slowest)
Thyroxine alters gene expression. Higher thyorixne levels means more alpha expression for alpha isoforms of the heavy chains of thick filaments. Thus more V1 and thus faster contraction!
Mice have way more expression of alpha and more a-a (v1) isoforms for faster heart rate
Humans have more beta expression and a slower heart rate
If you don’t have much thyroxine, you have a slower heart rate.
Define intercalated disk
Intercalated disk: connects cells together
Describe the light chains of thick filaments
2 pairs. Regulatory or phosphorylatable role.
Regulates ATP hydrolysis and phosphorylation
Define: polycythemia
increased hematocrit