10. Biochemistry II - Contractility Flashcards
in the RESTING STATE are CARDIAC MUSCLE CELLS polarised or depolarised and why
POLARISED (about -90mv)
inside negative as POTASSIUM CHANNELS are OPEN
- K+ EFFLUX
how are MYOSIN and ACTIN BOUND in RELAXED STATE
WEAKLY BOUND
- MYSOIN HEAD COCKED
- TROPOMYOSIN PARTIALLY BLOCKS BINDING SITE on actin
how is MYOSIN enabled to BIND STRONGLY to ACTIN and cause actin filament to MOVE during CONTRACTION
CA2+ BINDS TROPONIN
TROPONIN-CA2+ COMPLEX PULLS TROPOMYOSIN away from binding site so it is exposed
during RELAXATION, CA2+ is PUMPED BACK INTO SR via a CALCIUM ATP-ASE. this transporter is CONTROLLED by a PROTEIN called…
PHOSPHOLAMBAN
ACTION POTENTIALS begin in SA NODE. what is the name of the CELLS in the SA node that SPONTANEOUSLY FIRE action potentials
AUTORHYTHMIC CELLS
ACTION POTENTIALS generated in AUTORHYTHMIC CELLS SPREAD from cells to cells through …. between adjacent cardiomyocytes
GAP JUNCTIONS and INTERCALATED DISCS
In SAN NA+ channels that cause DEPOLARISATION (unstable resting potential) are called If (FUNNY) CHANNELS. these belong to a family of …. channels
HCN CHANNELS
- HYPERPOLARISATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED Channels
If (FUNNY) CHANNELS are PERMEABLE to BOTH…
NA+ and K+
when SA NODE DEPOLARISES the signal TRAVELS to AV NODE via which PATHWAYS
INTERNODAL PATHWAYS
from AV node through AV bundles and bundle branches to the apex of the heart
- purkinje fibres transmit impulses very rapidly so that cells in apex contract nearly simultaneously
P wave of ECG represents ATRIAL DEPOLARISATION. what does the LATTER PART of P WAVE represent which continues through the P-R / P-Q SEGMENT
START of ATRIAL CONTRACTION
Slows during P-R SEGMENT as passes through AV NODE
the SIGNALS TRAVEL through the BUNDLE BRANCHES to the APEX, takes place in which ECG WAVE
Q WAVE
which part of the BRAIN contains the CARDIOVASCULAR CENTRE
MEDULLA OBLONGATA
which AUTONOMIC NERVOUS SYSTEM causes DECREASE in HEART RATE
PARASYMPATHETIC
PARASYMPATHETIC NERVOUS SYSTEM DECREASES HEART RATE via which NERVE
VAGUS NERVE
SYMPATHETIC NERVOUS SYSTEM INCREASES HEART RATE via which NERVE
ACCELERATOR NERVE
which HIGHER BRAIN CENTRES input into CARDIOVASCULAR CENTRE (medulla oblongata)
CEREBRAL CORTEX, LIMBIC SYSTEM and HYPOTHALAMUS
input to CARDIOVASCULAR SYSTEM in medulla to moderate heart rate via which SENSORY RECEPTORS
PROPRIOCEPTORS - monitor movements
CHEMORECEPTORS - monitor blood chemistry
BARORECEPTORS - monitor blood pressure
PARASYMPATHETIC NERVES DECREASE HEART RATE via which HORMONE and which RECEPTORS does it act on
ACETYLCHOLINE
on MUSCARINIC RECEPTORS
SYMPATHETIC NERVES INCREASE HEART RATE via which HORMONR and which RECEPTORS does it act on
NORADRENALINE (norepinephrine)
on BETA-1 RECEPTORS
SYMPATHETIC NERVOUS SYSTEM CONTROLS which components of the HEART
ALL
PARASYMPATHETIC NERVOUS SYSTEM CONTROLS which components of the HEART
SA NODE & AV NODE
SYMPATHETIC NERVOUS SYSTEM INCREASES HEART RATE meaning it is POSITIVELY ….
CHRONOTROPIC
SYMPATHERIC NERVOUS SYSTEM INCREASES CONTRACTILITY meaning it is POSITIVELY ….
INOTROPIC
PARASYMPATHETIC NERVOUS SYSTEM is NEGATIVELY …
CHRONOTROPIC
PARASYMPATHETIC NERVOUS SYSTEM has what effect on CONTRACTILITY
LITTLE EFFECT
PARASYMPATHETIC NERVOUS SYSTEM (using vagus nerve and releasing Ach) DECREASES HEART RATE by doing what to the IMPULSE
PROLONGS the DELAY at the AV NODE
which NERVOUS SYSTEM controls the SA and AV NODES of the HEART
PARASYMPATHETIC
PARASYMPATHETIC NS releases ACH which acts on MUSCARINIC RECEPTORS of the AUTORHYTMIC CELLS.
what does it cause in order to HYPERPOLARISE the cell (ion movement) (and DECREASE the RATE of DEPOLARISATION)
INCREASED K+ EFFLUX
DECREASED CA2+ INFLUX
SYMPATHETIC NS releases NORADRENALINE which acts on BETA-1 RECEPTORS of AUTORHYTHMIC CELLS.
what does it cause in order to INCREASE RATE of DEPOLARISATION (ion movement)
INCREASES NA+ and CA2+ INFLUX
Sympathetic ns
when NORADRENALINE BINDS to BETA-1 RECEPTORS what does it ACTIVATE
cAMP - SECOND MESSENGER system
-> ACTIVATION of PROTEIN KINASE A
Sympathetic ns
NORADRENALINE BINDING to BETA-1 RECEPTORS ACTIVATES cAMP and PROTEIN KINASE A which PHOSPHORYLATES….
Voltage-Gated CA2+ CHANNELS and PHOSPHOLAMBAN
Sympathetic nervous system releases noradrenaline -
PHOSPHORYLATION of Voltage-Gated CA2+ CHANNELS causes…. which leads to MORE FORCEFUL CONTRACTIONS
INCREASE in their OPEN TIME
INCREASE CA2+ ENTRY
INCREASES CA2+ STORES in SR
& INCREASES CA2+ RELEASED
therefore more forceful contractions
what EFFECT does PHOSPHOLAMBAN have on CA2+-ATPase
INHIBITOR of it
Sympathetic NS
Activated PROTEIN KINASE A also PHOSPHORYLATES PHOSPHOLAMBAN which does what in order to SHORTER DURATION of CONTRACTION
RELIEVES INHIBITION effect on ca2+-ATPase
INCREASES CA2+-ATPase on SR
REMOVES CA2+ from CYTOSOL FASTER
- SHORTENS CA-TROPONIN BINDING TIME
shortens contraction duration
Sympathetic NS
Activated PROTEIN KINASE A also PHOSPHORYLATES PHOSPHOLAMBAN which does what in order to create MORE FORCEFUL CONTRACTIONS
INCREASES CA2+-ATPase on SR
INCREASES CALCIUM STORES in SR
and so INCREASES CALCIUM RELEASE
therefore more forceful contractions
what are the 2 possible CALCIUM REGULATED CARDIAC SIGNALLING PATHWAYS
- by DEPOLARISATION
- by STIMULATION via ADRENERGIC RECEPTORS (BETA-1) (sympathetic nervous system)
BETA-1 RECEPTORS that BIND NORADRENALINE are what type of RECEPTORS
ADRENERGIC RECEPTORS
- G-PROTEIN COUPLED
CO = SV X HR
at REST what is the AVERAGE CO in adults
4.9 litres per min
what is the EQUATION for STROKE VOLUME (amount of blood transferred from left ventricle to arterial system during systole)
SV= EDV (END DIASTOLIC VOLUME) - ESV (END SYSTOLIC VOLUME)
EDV - total volume of blood in the ventricle at the end of diastole, dependent on PRELOAD
ESV - volume of blood remaining in ventricle at end of Systole, Dependent on AFTERLOAD
STOKE VOLUME is DETERMINED by which 3 FACTORS
- PRELOAD: the initial STRETCHING of cardiac myocytes before contraction, related to ventricular filling
- CONTRACTILITY: force that the muscle can generate at any given length
- AFTERLOAD: the ARTERIAL PRESSURE against which the muscle will contract
what is EJECTION FRACTION (EF)
AMOUNT OF BLOOD PUMPED OUT OF VENTRICLE (SV)
/
TOTAL AMOUNT OF BLOOD IN VENTRICLE (EDV)
= SV / EDV x 100
what is the NORMAL/HEALTHY EJECTION FRACTION range - what proportion of the blood in the ventricle should be pumped out
50-65%
what is PRELOAD
the DEGREE of MYOCARDIAL STRETCH caused by END-DIASTOLIC VOLUME
this stretch represents the load placed on cardiac muscles before they contract
- increased EDV stretches the heart
- cardiac muscles stretch and contract MORE FORCEFULLY, ejecting MORE BLOOD (FRANK STARLING LAW)
AFTERLOAD refers to the amount of ..
RESISTANCE / PRESSURE that the heart must PUMP AGAINST
during systole
determined by VASCULAR RESISTANCE
VASOCONSTRICTION will have what effect on AFTERLOAD
INCREASE AFTERLOAD PRESSURE
PRELOAD is influenced by which factors
- VENTRICULAR FILLING
- FILLING TIME
CONTRACTILITY is influenced by which factors
- AUTONOMIC INNERVATION
- HORMONES
AFTERLOAD is influenced by which factors
- VASODILATION / VASOCONSTRICTION
what does the FRANK-STARLING LAW state
that the STRENGTH of VASCULAR CONTRACTION is DEPENDENT of the LENGTH of the RESTING FIBRES (due to myocyte STRETCH)
- INCREASE in LEFT VENTRICULAR PRELOAD causes STROKE VOLUME to INCREASE
without the need for extrinsic neural or hormonal regulatory mechanisms
the STARLING CURVE defines the …… RELATIONSHIP in the intact HEART
LENGTH-FORCE RELATIONSHIP
increase STRETCH (indicated by EDV), increases FORCE (indicated by SV)
as more stretch means MORE TENSION in muscle fibres
besides STARLING LAW and STRETCH/PRELOAD, what also INCREASES CONTRACTILITY
SYMPATHETIC STIMULATION
- ADRENALINE
how is FRANK-STARLING RELATIONSHIP in HEART FAILURE
DAMAGED MYOCYTES - LESS STRETCH (stiffness)
- REDUCTION in PRELOAD
-> REDUCTION in STROKE VOLUME
molecular changes in cardiac cells cause decreased active (systolic) force and impaired (diastolic) relaxation together with a greater stiffness of the remodelled ventricular wall
