Contractility Flashcards
What controls SV?
preload, HR, contractility, afterload
How does preload control SV?
Stretching of heart at rest, increases SV due to Starling’s law
How does HR control SV?
Sympathetic + parasympathetic nerves
How does contractility control SV?
Strength of contraction at given resting load, due to sympathetic nerves + A increasing [Ca2+ ]
How does afterload control SV?
Opposes ejection, reduces SV due to Laplaces law
What does the electrical graph show?
- electrical stimulation, depolarisation
- brief increase in Ca2+ signal inside cell
- stays elevated
- cell shortening (contraction)
- down repolarisation
- reduced Ca2+ signal –> relax
What’s the diff between preload vs contractility?
preload is what’s the stretch of RESTING cardiac tissue
contractility is strength of contraction at any given stretch due to sympathetic
What’s the force of contraction proportional to?
rise in (intracellular) Ca2+
What’s the diastolic, normal + max systolic [Ca2+]?
100Nm
1μM
10μm
What’s the inotropic effect?
Increase in contractility due to rise in [Ca2+]
Why doesn’t the cardiac muscle do all or nothing?
enables change in SV by changing contractility
Why is normal cell shortening sub-maximal?
resting enough for proper ejection but can do more when exercise
How does electrical excitability contract cardiac myocytes?
- atrial/ventricular AP
- plateu phase - opening vgcc
- Ca2+ influx 2μM to 100nM
- Ca2+ acts as ligand at ligand gated receptor on sarcoplasmic reticulum (Ca2+ store)
- Ca2+ binds to RyR (ligand gated ion channel on sarcoplasmic reticulm surface) CICR
- Ca2+ out of store to cytosol
What 2 ways cause Ca2+ rise from 0.1μM to 10μM in cell?
Ca2+ influx from AP
CICR
What are T tubules?
invaginations of membrane
contains Na+ channels + vgcc inside
underneath it is SR, actin + myosin
Why does Ca2+ rise so quickly?
contricted v in subsarcolemic space
Describe the rise in Ca2+ in sub-cellular?
- AP (Na+) depolarises T-tubules
- vgcc activated, local Ca2+ influx
- Ca2+ binds to RyR on SR
- release of Ca2+ from SR (CICR)
- Ca2+ to troponin, displacement of tropomyosin/troponin complex, exposing active sites
- myosin heads bind to active sites
- myosin head ATPase activity release energy (ATP to ADP)
- slide filaments - contraction
How does rise in Ca2+ produce actin-myosin interaction?
- Ca2+ binds to TnC
- displaces tropomyosin/TnI so binding sites exposed + actin-myosin cross-bridge formed
- myosin head flexes moving actin + Z line towards sarcomere centre
- contraction – ATPase activity
How does troponin indicate cardiac cell death/MI?
TnI + TnT released from cell into plasma
Function of TnT?
binds to Tropomyosin
Function of TnI?
binds to actin filaments to hold tropomyosin in place
Function of TnC?
binds Ca2+
Describe decrease in Ca2+ in sub-cellular?
- AP (K+) repolarises T-tubules
- closes vgcc, no Ca2+ influx, no CICR
- extrusion of Ca2+ (30%) by Na+/Ca2+ exchanger on membrane (NCX)
- Ca2+ uptake into SR via SR Ca2+-ATPase (SERCA, 70%) – recycled for next contraction
- uptake of Ca2+ in mitochondria
- myosin head ATPase activity release energy (ATP to ADP)
- chambers relaxed - fill w blood
How does the Na+/Ca2+ exchanger on membrane (NCX) work?
1 Ca2+ out for 3 Na+ in
Why’s cardiac muscle suscpetible for drop in O2/metabolite?
SR has Ca2+-ATPase (SERCA) uses ATP to move Ca2+ from cytosol to SR for relaxation + CICR
Diff between Inotropy vs Starling’s law?
Inotropy : same resting p/v, extrinsic control – due to rise in [Ca2+]
Starling’s law : increased resting p/v + energy of contraction, intrinsic stretch
Both increase SV in diff ways but inotropy increases it more
What does NA do?
Acts on β1 adrenoceptors on myocytes to increase contractility
How does stimulation of β1 adrenoceptors increase contractility?
-NA binds to β1 (Gs) - activate adenyl cyclase producing cAMP from ATP
-cAMP -> PKA
-PKA phophorylates vgcc on membrane + RyR on SR:
vgcc opens often, more Ca2+ influx
RyR more active, greater CICR
-GREATER RISE IN Ca2+ —> contractility
How does stimulation of β1 adrenoceptors induce relaxation?
- NA binds to β1 adrenoceptor (Gs) - activate adenyl cyclase producing cAMP from ATP
- cAMP -> PKA
- PKA phosphorylates K+ channels on membrane
- K+ channels switched on
- K+ efflux
- cell repolarises quicker so switches off vgcc quicker
- PKA stimulates SERCA
- more Ca2+ reuptake
- DECREASE IN Ca2+ —> relaxation
How does sympathetic stimulation relate to cardiac AP?
↑depolarisation, repolarisation, HR, conduction
Why does next AP come quicker with sympathetic stimulation?
↑HR as sympathetics affect SAN
How does sympathetic stimulation relate to contraction-relaxation?
↑force of contraction, relaxation, Ca2+ store
How’s the diastolic time maintained with sympathetics?
shortening AP + contraction time
Why does the diastolic time need to be maintained?
- chambers fill w blood
- maintain coronary perfusion
Define positive inotropic effect
↑ contractility
Due to vgcc/Ca2+ influx + RyR/CICR
Define positive chronotropic effect
↑ HR
Due to pacemaker potential freq at SAN
Define positive dromotropic effect
↑ conduction at AVN + between cardiac muscle cells
Define positive lusitropic effect
↑ rate of relaxation
Due to more K channels + SERCA, less vgcc
What are negative inotropic agents?
High external [K+]
Increased [H+]
Low O2 levels
What’s the effect of hyperkalaemia?
- high external K+ from 3.5-5 mM to 7-8mM
- depolarises membrane potential in cardiac tissue
- Na+ channels become inactivated conc
- reduces onset time/amplitude/shorter AP
- heart in refractory mode
- heart failure
What’s the effect of low pH?
- H+ compete for Ca2+ on Tc binding sites
- no actin-myosin interaction
- no contraction
What’s the effect of hypoxia?
- no oxidative phosphorylaton so anerobic
- lactic acid –> local acidosis
- depolarises membrane potential so smaller/shorter AP -poor contraction
