Transcript Mechanisms of Myocardial Contraction

Mechanisms of Myocardial
Contraction
Dr. B. Tuana
Heart Structure
• Heart Consists of 2
Independent parallel
pumps
• The Right Side is
Responsible for
Pulmonary Circulation
• The Left Side is
Responsible for
Systemic Circulation
Cardiac Phases
• There are 2 Principle Phases in the Cardiac Cycle
• Systolic Phase (lasting ~0.3 sec) is the phase of
contraction of the heart. This requires the most
energy.
• Diastolic Phase (lasting ~0.5 sec) is a phase of
relaxation and filling of the heart.
• During the diastolic phase, the cardiocyte`s
supply of nutrients replenished
ATP
• The energy that myocytes need to contract
during the systolic phase comes from ATP
• ATP Can be generated from either oxidative
phosphorylation or glycolysis
ATP From Oxidative Phosphorylation
• Under normal conditions (when adequate O2 is
present), the oxidative phosphorylation pathway
predominates.
• Occurs entirely within the mitochondria (abundant in
heart)-differs from skeletal muscle (fatigue?)
• Both fats and CHO enter the mitochondria as 2carbon fragments which are then oxidized to CO2 and
H2O
ATP From Oxidative Phosphorylation
• Free Fatty Acids bound to albumin in
plasma are taken into myocyte
• Plasma TG's are hydrolyzed by lipase to
FFA's. Lipase activity is regulated by
hormones.
Myocardial Oxygen Consumption
(MV02)
• Cardiocytes require large amounts of oxygen to
generate ATP from Aerobic metabolism.
• ~75% of MV02 is for contraction of myocytes.
• ~25% of MV02 is for other cellular processes (ion
transport)
• Disease states increase MV02 to a point where
myocytes become ischemic. (eg Coronary Artery
Disease).
ATP From Glycolysis
• Glycolysis is essential for aerobic
carbohydrate breakdown
• Allows ATP to be generated under
Anaerobic Conditions
Substrates Used for ATP Production
• ~% oxygen utilized.
• ~Normal Conditions: (100%) O2, free fatty acids (70%),
glucose (15%) and lactate (15%).
• ~Hypoxia: mainly glucose (from glycogen, anaerobic)
• ~Hyperlipidemia: triglycerides (~50%), FFA (~30%)
• ~CHO loading: glucose (~70%), lactate (~30%)
• ~Diabetics, Starvation: ketones (~70%), FFA (30%)
• ~Exercise: lactate (~60%), glucose (~15%), FFA (20%)
Carbohydrate Breakdown
Fatty Acid Breakdown
ATP PRODUCTION IS TIGHTLY
COUPLED TO MECHANICAL ACTIVITY:
• Hormones (epi, norepi) increase mechanical work
• Hormones also increase ATP production via...increased
glycolysis, glycogen mobilization and FFA production
• ADP concentration can control rate of ATP synthesis by
oxidative phosphorylation
• Increased cardiac activity, increases ATP breakdown to
ADP...which stimulates oxidative phosphorylation
pathways to make more ATP.
• A Decrease cardiac activity leads to excess ATP...which
inhibits further ATP synthesis
Excitation Contraction Coupling
in Cardiac Muscle
• Action potential
propagated along
muscle cell membrane
(sarcolemma)
• Sarcolemma possesses
deep invaginations
referred to as T-tubules
• Calcium induced
calcium release
• Intercalated discs-gap
junctions, force
transmission
Excitation-contraction in cardiomyocytes
Excitation Contraction Coupling
in Cardiac Muscle
• Propagating action potential opens Voltage
gated Ca2+ channels
• The intracellular concentration of Ca2+ rises
which triggers further release of Ca2+ from
the sarcoplasmic reticulum (SR)-contraction
• Inotropy (inotropic agents + or -)
• Ca2+ ATPase in SR (Ca2+ uptake)relaxation
Stimulation of contraction by
adrenergic stimulation in heart cells
Stimulation of Contraction by
adrenergic stimulation
Stimulation of Contraction by
adrenergic stimulation
Excitation Contraction Coupling
in Cardiac Muscle
• Involves Interaction between actin and
Myosin
• Thick filaments (Myosin) utilize ATP to
slide over thin (actin) filaments
• Involves the activity of several regulatory
proteins (ie troponin, tropomyosin)
Excitation Contraction Coupling
in Cardiac Muscle – Actin and Myosin
• Principle proteins of muscle contraction
• Actin has a binding site for myosin
• Myosin has a ATP hydrolysing domain, and
an actin binding site
• The regulatory proteins troponin and
tropomyosin are associated with actin
Excitation Contraction Coupling
in Cardiac Muscle – Troponin and
Tropomyosin
• Tropomyosin is a long protein associated
with actin that covers the actin binding site
in the resting state
• Troponin lies at regular intervals along the
actin filament. Troponin mediates the
activity of tropomyosin
• Troponin is sensitive to levels of Ca2+
Excitation Contraction Coupling
in Cardiac Muscle
• As the intracellular concentration of Ca+2
rises troponin is activated.
• The activated troponin triggers tropomyosin
to undergo a conformational change.
• This conformational change exposes the
myosin binding site on actin
The Contractile Process
ATP
Power Stroke