Force generation by the heart (CVS4) Flashcards
what is the striation of heart muscle caused by
regular arrangement of contractile protein
As there are no neuromuscular junctions in the cardiac muscle, how are the cardiac myocytes electrically coupled
- by gap junctions (protein channels which form low resistance electrical communication pathways between neighbouring myocytes)
- they ensure that each electrical excitation reaches all of the cardiac myocytes (all or none law of the heart)
neuromuscular junction
connection between a nerve cell and a muscle, where nerve impulses are transmitted to initiate contraction of the muscle
myocyte
contractile muscle cell
function of desmosomes within intercalated discs
- provide mechanical adhesion between adjacent cardiac cells
- ensure that the tension developed by one cell is transmitted to the next
how is the tension developed in a muscle cell (sliding filaments theory)
- muscle tension is produced by sliding of actin filaments on myocin filaments
- the sliding filaments theory is the explanation how muscle shortens and produces force
- force generation depends upon ATP-dependent interaction between thick (myocin) and thin (actin) filaments
- ATP is required for both contraction and relaxation
- Ca++ is required to swtich on cross bridge formation which join the two types of filaments together
- within the sarcomere, actin, and myosin filaments are arranged in parallel and slide past each other to cause shortening. The interaction of myosin with actin is controlled by the actin-binding proteins tropomyosin and troponin
- At low Ca2+ concentrations, troponin locks tropomyosin in a position where it obstructs the myosin-binding site, thus preventing contraction of the sarcomere
- When Ca2+ binds to troponin, tropomyosin moves on the actin filament, exposing the myosin-binding site. -Myosin attaches to the actin filament and performs a power stroke, which results in shortening of the sarcomere
myofibrils
- each muscle fibre/cell contains many myofibrils
- these are the contractile units of the muscle
- the myofibrils have alternating segments of thick/thin protein filaments (actin is thin, myocin is thick)
actin
- thin filaments
- causes lighter appearance in myofibrils/fibres
myocin
- thick filaments
- cause darker appearance in myofibrils/fibres
sacromeres
- basic functional unit of striated muscle
- within each myofibril, actin and myocin are arranged into sacromeres
structure of striated muscle fibre
- each fibre contains many myofibrils/contractile units
- myofibrils have alternating segments of thick (myocin) and thin (actin) protein filaments
- actin causes lighter appearance in myofibrils/fibres
- myocin causes darker appearance
- myocin and actin arranged into sacromeres within each myofibril
Ca++ release in cardiac muscle
- Ca++ is released from the sarcoplasmic reticulum (SR)
- in cardiac muscle the release of Ca++ from SR is dependent on the presence of extra-cellular Ca++
- action potential in muscle cell causes release of Ca++ from the SR and this causes the myosin fibrils to ‘ratchet’ across the actin fibrils, shortening the sarcomere.
- calcium levels must be restored following contraction
- use ATP energy to pump it back into the lateral sacs of the sarcoplasmic reticulum
steps involved in joining of actin and myosin
- ATP is required for both contraction and relaxation
- in the energized state (when ADP +Pi is present) but no Ca++ is present, actin and myosin do not join by cross bridge and go into resting state (troponin blocks mysosin binding site on actin by locking tropomyosin to it)
- presence of Ca++ causes excitation, Ca++ binds to troponin and tropomyosin moves from binding site and binding occurs between actin and myosin via crossbridge (Ca++ is required to swtich on cross bridge formation which join the two types of filaments together) (prepower stroke= ADP/Pi-bound state of actin and myosin)
- Myosin attaches to the actin filament and performs a power stroke, which results in shortening of the sarcomere
- when energy is removed from the complex/there is no ATP available after death, rigor complex exists
- if fresh ATP is made available the complex detach
- and once ADP/Pi are taken up by myosin, they are in the energized state once again
- > in relaxed phase, troponin is bound to actin along with tropomyosin, however actin and myosin have not joined via cross bridges as Ca++ is not present
- > in excited phase, Ca++ is present and cross bridge formation is turned on between actin and myosin as Ca++ binds to troponin and moves tropomyosin from myosin binding site of actin
rigor complex
- A chemical complex formed between myosin and actin during a muscle action. In the rigor complex, the myosin head is bent to the 45° position and is bound to actin. -Unbinding of the head requires ATP and removal of calcium bound to troponin so that tropomyosin can prevent the myosin head from binding to the actin, to allow muscle to relax
- Muscle cramps may be due to the development of a rigor complex, either because of lack of ATP or an inability to remove calcium
why are skeletal muscle described as striated? (histological explanation from histology notes)
Because viewed under the microscope the fibres have a regular pattern of bands running across the fibre at right angles to the long axis. This is also true for cardiac muscle. This is because the sarcomeres in the myofibrils are held in registry with one another, that is, the Z-disks in the sarcomere of one myofibril will be lined up with the Z-disks of the sarcomeres in the adjacent myofibrils.
sarcoplasmic reticulum (histological explanation)
the endoplasmic reticulum of a striated muscle fiber that regulates the concentration of calcium ions in the cell cytoplasm
T-tubules (histological explanation)
Within the muscle cell an extensive network of tubules, called transverse tubules or T-tubules extend from the sarcolemma into the cell, ramifying and surrounding each myofibril roughly at the A (band)-(I) band junction of each sarcomere
different types of bands/lines of striated muscle fibres
- A band – (dArk) myosin (thick) filaments stacked along with parts of the actin (thin) filaments
- M line - extends vertically down the Middle of the A band
- I band – (lIght) part of actin that does not project into A band
- H zone - centre of the A band where actin does not reach
- Z line – site of attachment of thin filaments
sliding filaments theory in regard to bands of striated muscle fibre
- Due to interactions of thin and thick filaments, the filaments slide over one another. The filaments themselves do not get smaller
- A band – determined by thick filaments so stays same size
- I band – thin filaments not overlapping thick, so decreases
- H zone – within A band, thick filaments not overlapping thin so decreases
- Distance between Z lines – decreases
protein components of thick and thin filaments
- thick filament=myosin tail and myosin head
- thin filament=actin, troponin and tropomyosin (The main structural component of a thin filament is two chains of spherical actin molecules that are twisted together. Troponin molecules (which consist of three small, spherical subunits) and threadlike tropomyosin molecules are arranged to form a ribbon that lies alongside the groove of the actin helix and physically covers the binding sites on actin molecules for attachment with myosin cross bridges. (Thick filaments are two to three times larger in diameter than thin filaments.)
tropomyosin in relaxed muscle
In relaxed muscle - tropomyosin masks the
myosin-binding site on the actin filament, therefore no cross bridge binding
cross bridges
formed by globular head of myosin molecules
different stages of cross bridge activity (steps involved in a single cross bridge cycle)
1-binding = mysosin cross bridge binds to the actin molecule
2-power stroke= cross bridge bends, pulling thin myofilament inward
3-detachment= cross bridge detaches at end of power stroke and returns to original conformation
4-binding = cross bridge binds to a more distal actin molecule; cycle repeats
-The power strokes of all cross bridges extending from a thick filament are directed toward the center of the thick filament
-All six thin filaments surrounding each thick filament are pulled inward simultaneously through cross-bridge cycling during muscle contraction. (on cross section of a myofibril, you can see each thick filament is surrounded by six thin filaments, and each thin filament is surrounded by three thick filaments)
cross bridge cycle in words (from abbi’s previous notes)
1- ATP split by myosin ATPase; ADP and Pi remain attached to myosin; energy stored in cross bridge
2a- Ca++ released on excitation; removes inhibitory influence from actin, enabling it to bind with cross bridge
or 2b- no excitation; no Ca++ released; actin and myosin prevented from binding;no cross bridge cycle;muscle fibre remains at rest
3-power stroke of cross bridge triggered on contact between myosin and actin; Pi and ADP are released
4a-linkage between actin and myosin broken as fresh molecule of ATP binds to myosin cross bridge; cross bridge assumes original conformation; ATP hydrolyzed (cycle starts again at step 1)
or 4b- if no fresh ATP available (after cell death), actin and myosin remain bound in rigor complex
how does the ventricular action potential switch on ventricular systole/contraction
- action potential in muscle cell causes release of Ca++ from the SR and this causes the myosin fibrils to ‘ratchet’ across the actin fibrils, shortening the sarcomere
- Ca++ influx during plateau phase of action potential
- Ca++ activates contractile machinery (contracts via sliding filaments theory)
- Ca++ - induced Ca++ release (CICR-calcium induced calcium release) from SR (in cardiac muscle the release of Ca++ from SR is dependent on the presence of extra-cellular Ca++, therefore the Ca++ influx into the sarcolemma causes the release of more Ca++ from the SR)
- once the action potential has passed, Ca++ is taken up again in the SR and hidden away, by Ca++-ATPase, and the heart muscle relaxes
ventricular diastole
- ventricular muscle relaxes
- Ca++ outside sarcolemma ~2x10-3 M
- resting Ca++ levels inside sarcolemma
sarcolemma
the fine transparent tubular sheath that envelops the fibers of skeletal muscles
ventricular sytole
- ventricular muscle contracts
- Ca++ influx during plateau phase of action potential (through voltage Ca++ channels)
- Ca++ activates contractile machinery (contracts via sliding filaments theory)
- Ca++ - induced Ca++ release (CICR-calcium induced calcium release) from SR (in cardiac muscle the release of Ca++ from SR is dependent on the presence of extra-cellular Ca++, therefore the Ca++ influx into the sarcolemma causes the release of more Ca++ from the SR)
- once the action potential has passed, Ca++ is taken up again in the SR and hidden away, by Ca++-ATPase, and the heart muscle relaxes
what triggers power stroke
binding of actin and myosin cross bridge triggers power stroke that pulls the thin filament inward during contraction
importance of long refractory period to normal cardiac function
- protective for the heart
- prevents generation of tetanic contraction (a condition of continuous contraction)
refractory period
-period following an action potential in which it is not possible to produce another action potential
plateau phase of ventricular action potential
Na+ channels are in the depolarized closed state ie. they are not available for opening
descending phase of ventricular action potential
K+ channels are open and the membrane can not be depolarized
stroke volume (SV)
- the volume of blood ejected by each ventricle per heart beat/contraction
- contraction of the ventricular muscle ejects this
- SV= end diastolic volume (EDV) - end systolic volume (ESV)
how is stroke volume regulated
-by intrinsic and extrinsic mechanisms
intrinsic mechanisms of the heart
- within the heart itself
- related to extent of venous return
extrinsic mechanisms of the heart
- nervous and hormonal control
- related to extent of sympathetic stimulation of the heart
intrinsic control/regulation of stroke volume
what causes changes in stroke volume
- changes in stroke volume are brought about by changes in the diastolic length of myocardial fibers
- maximal force is generated at optimal fibre length
what determines diastolic length of myocardial fibres
- end diastolic volume (volume of blood within each ventricle at the end of diastole)
- main determinant is the degree of diastolic filling
- increased EDV, the more the heart is stretched, the more the heart is stretched the longer the initial cardiac fibre length before contraction, this increased length results in a greater force on the subsequent cardiac contraction and thus results in a greater stroke volume (this intrinsic relationship is known as the frank starling law of the heart)
what determines cardiac preload
end diastolic volume
end diastolic volume
- volume of blood within each ventricle at the end of diastole
- determined by venous return to the heart
- end diastolic volume determines cardiac preload
Frank starling mechanism/ starling’s law of the heart
- describes the relationship between venous return, end diastolic volume and stroke volume
- it states that the more the ventricle is filled with blood during diastole (end diastolic volume), the greater the volume of ejected blood will be during the resulting systolic contraction (stroke volume)
- The heart normally pumps out during systole the volume of blood returned to it during diastole; increased venous return results in increased stroke volume
why does an increase in EDV result in an increase in SV
- because intrinsic control of the heart depends on the direct correlation between EDV and SV
- as more blood returns to the heart, the heart pumps out more, although the heart does not eject all the blood it contains
preload
The extent of filling is referred to as preload because it is the workload imposed on the heart before contraction begins
what does the stretch of the cardiac muscle (due to increase in EDV) also increase as a result
affinity of troponin for Ca++
difference in optimal fibre length in skeletal and cardiac muscle
- in skeletal muscle the optimal fibre length at resting muscle length
- in cardiac muscle the optimal fibre length is achieved by stretching the muscle
how does starlings law ensure SV of right and left ventricles match
- if venous return to the right atrium increased, EDV of right ventricle increase
- starlings law leads to increased SV into pulmonary artery
- venous return to the left atrium from pulmonary vein increases, EDV of left ventricle increases
- starlings law leads to increased SV into aorta
afterload
- resistance into which the heart is pumping
- the extra load is imposed AFTER the heart has contracted
how does frank starling mechanism/starlings law of the heart partially compensate for decreased SV caused by increased afterload
- at first, heart is unable to eject full SV, so EDV increases
- force of contraction rises by frank starling mechanism (increase in EDV increases SV and force is increased to eject this)
- if increased afterload continues to exist (eg. untreated hypertension) eventually the ventricular muscle mass increases (ventricular hypertrophy) to overcome the resistance
extrinsic control of stroke volume
- this involves nerves and hormones
- the ventricular muscle is supplied by sympathetic nerve fibres
- neurotransmitter=noradrenaline
- stimulation of sympathetic nerves increase the force of contraction (positive inotropic effect, also causes positive chronotropic effect-increase in HR)
inotropic effect
- relates to force of contraction
- increase in sympathetic nerves causes a positive inotropic effect
inotropic effect of noradrenaline on ventricular contraction
presence/increase in noradrenaline causes an increase in ventricular pressure/pressure also rises quicker
effect of sympathetic stimulation on ventricular contraction
- force of contraction increases (activation of Ca++ channels-greater Ca++ influx)
- effect is cAMP mediated
- peak ventricular pressure rises
- rate of pressure change during dP/dt (diastolic pressure/diastolic time)
- this reduces duration of systole
- rate of ventricular relaxation increases (increased rate of Ca++ pumping)
- this reduces duration of diastole
effect of sympathetic nerve stimulation on ventricular contraction
- peak ventricular pressure rises (contractibility of heart at a given EDV rises)
- frank starling curve is shifted to the left
effect of heart failure on frank starling curve
shifts curve to the right
effect of positive/negative inotropic agents on ventricular contraction
- positive inotropic effect shifts curve to left
- negative inotropic effect shifts curve to right
effect of parasympathetic nerves on ventricular contraction
- very little innervation of the ventricles by vagus therefore little, if any effect on SV
- vagal stimulation has major influence on rate, not on force of contraction
extrinsic control of SV (hormones)
- adrenaline and noradrenaline released from adrenal medulla have inotropic and chronotropic effect
- normally minor contraction force effects of noradrenaline from sympathetic nerves
Cardiac Output (CO)
- volume of blood pumped by each ventricle per minute
- CO=SV xHR
resting CO in healthy adult
approx. 5L per minute (70ml SV x 70 bpm = 4900ml CO)
how is cardiac output (CO) regulated
by regulating stroke volume and heart rate
