contractility Flashcards
What Controls Stroke Volume? (4)
How do they control SV?
Preload -Stretching of heart at diastole, increases SV - Starling’s law
Heart rate – Sympathetic and Parasympathetic Nerves
Contractility – Strength of contraction at a given resting loading, due to sympathetic nerves + circulating adrenaline increasing [Ca2+ ]i
Afterload – Opposes ejection, reduces SV - Laplaces law
how is rise in Ca2+ central to contraction?
significance?
Force of contraction proportional to rise in [Ca2+]i
Diastolic [Ca2+]i ~ 100 nM
Normal systole -> [Ca2+]i may rise ~ 1 M
Maximum systole, e.g. during vigorous exercise [Ca2+]i may rise ~ 10 M
why is the proportionate rise in Ca2+ important?
OR What is inotropic effect?
Normal cardiac contraction is sub-maximal
Increase in contractility due to larger rise in [Ca2+]I allow us to increase stroke volume and cardiac output
- called the Inotropic Effect -
levels of ca2+ with cell shortening and relaxation
what phase is cell shortening? cell relaxation
Plateau phase of action potential
Voltage-gated Ca2+ channels open -> Ca2+ influx
Rise in [Ca2+]i signal - cell shortening
Repolarisation of action potential -> Reduced Ca2+ signal
Cell relaxation
how does Rise in [Ca2+]i induce contraction
where does depolarisation take place? what is activated? what is closely associated with T-tubules? what is CICR? effect of this? where does Ca2+ bind? effect of this? how does contraction take place?
1) AP upstroke (Na+ ions) depolarises T-tubules – activation of VGCCs, local Ca2+ influx
2) Ca2+ binds to RyR located on SR - close association with T-tubules
3) Release of Ca2+ from SR (CICR)
4) Ca2+ to troponin, displacement of tropomyosin/troponin complex, exposing active sites
5) Myosin thick filament heads bind to active sites
6) Myosin head ATPase activity release energy (ATP to ADP)
7) Slide filaments - contraction
how does Rise [Ca2+]i cause myosin-actin interactions?
what blocks binding sites?
what displaces this? effect of displacement?
what constitutes as the contraction?
a) Myosin-actin binding sites blocked by troponin-tropomyosin complex
b) Ca2+ displaces troponin-tropomyosin :
actin-myosin binding sites exposed and actin-myosin cross-bridge formed
c) Myosin head flexes to move actin and Z line towards sarcomere centre :
Contraction – ATPase activity
why does a greater rise in Ca2+ lead to more contractility?
Greater rise in [Ca 2+]i leads to MORE Sites exposed And MORE Crossbridges formed hence MORE Contractility
what are troponin made up of in the troponin-tropomyosin complex?
how many subunits and what do they bind to?
Troponin - Composed of three regulatory subunits
TnT - binds to tropomyosin
TnI – binds to actin filaments to hold tropomyosin in place
TnC – binds Ca
how does rise in Ca2+ affect the troponin-tropomyosin complex?
Rise in Ca2+ leads to Binding of Ca to TnC
Leads to displacement of tropomyosin/TnI and exposure of actin binding sites
important blood markers following cardiac cell death
TnI and TnT important blood plasma markers for cardiac cell death
e.g. Following MI
How do you decrease Ca2+ at a sub-cellular level? (4)
how to stop influx?
how do you extrude it? which method of extrusion is more significant?
1) AP downstroke (K+ ions) repolarises T-tubules – closure of VGCCs, less Ca2+ influx
2) No Ca2+ influx, no CICR
3) Extrusion of Ca2+ from cell (30%) - by Na+/Ca2+ exchanger (NCX)
4) Ca2+ uptake into SR via SR Ca2+-ATPase (SERCA, 70%) – Ca2+ in SR for next contraction
how does decrease in Ca2+ affect heart muscle? effect of this on chambers?
Reduction in [Ca2+]i, tropomyosin-troponin system prevent myosin-actin interactions
Prevention of contraction mechanism – chambers relaxed, and can fill with blood
Difference between Starling’s Law and Contractility (Inotropy Effect)
what kind of control are they?
movement on the graph? why?
Starling Law goes right (→) in a graph as increased Resting pressure/volume returning to heart therefore increased Energy of contraction -> Starling’s Law - Intrinsic stretch
Introphic effect (contractility) goes up (↑) in a graph as Same resting pressure/volume and increased Contractility termed INOTROPY from Extrinsic control –> due to rise in [Ca2+ ]i
How can we increase cardiac contracitility via sympathetic nervous system?
what acts on what receptors?
effect of this? (4)
We produce an Inotropic Effect mostly through stimulation of Sympathetic Nervous System
Noradrenaline (NA) acts on B1-adrenoceptors to increase contractility AND ALSO increase relaxation, heart rate and conduction
How does stimulation of B1-adrenoceptors induce an increase contractility?
what binds to this receptor?
what pathway does it activate? hence effect of this?
2 effects of PKA? net effect of both these effects? and effect of this?
NA binds to B1-adrenoreceptors which activates the GaS pathway therefore ATP is converted into cyclic AMP by adenocyclase which activates protein kinase A
1) PKA phosphorylates VGCCs which leads to a Ca2+ influx
2) PKA phosphorylates RyR on SR which leads to release of Ca2+
Both pathways lead to more Ca2+ released via CICR
Huge increase on Ca2+ leads to more sliding filament mechanism hence MORE contractility
