cardiac contraction Flashcards
duration of AP
200-500ms
what is the force of contraction proportional to
[Ca2+]i
[Ca2+]i during systole
~1uM
[Ca2+]i at maximum contraction
~10uM
why doesn’t [Ca2+]i usually reach 10uM
Normally cell shortening is submaximal
what happens in the depolarisation phase
ca signal and cell shortening - when Ica is generated
what happens in the repolarisation phase
cell relaxation - when ca2+ signal is reduced.
what is contraction determined by
INCREASE in IC Ca2+ levels
what does a higher increase in [Ca2+]i lead to
increased force of contraction
how does [Ca2+]i change
from 0.1uM to about 10uM
which receptor does calcium active on the sarcoplasmic reticulum
Ryanodine / calcium induced calcium release (CICR)
what causes Ca release from SR
(AP upstroke) Na+ ions depolarise T tubules, activating VDCCs, allowing Ca2+ influx
Ca binds to RyR /CICR on SR - close association with T tubules
Release of Ca from SR
How does rise in [Ca2+]i cause myosin-actin interactions
Originally my-ac binding sites blocked by troponin-tropomyosin complex;
ca2+ displaced troponin-tropomyosin;
binding sites exposed, cross bridge formed;
myosin head flexes to move actin and Z line to sarcomere centre: contraction
what is troponin made up of
TnT - binds to tropomysoin
TnI - binds to actin to hold tropomyosin in place
TnC - binds Ca
how does tropomysoin get displaced
binding of Ca to TnC subunit, exposing actin binding sites
Other clinical significance of TnI and TnT
important plasma markers for cardiac cell death
how does decrease in [Ca2+]i occur
(AP downstroke) K+ ions repolarise T tubules - VDCCs close, decrease in Ca influx;
no Ca influx, no CICR; extrusion of Ca from cell (30%) by Na/Ca exchanger
Where does Ca uptake occur in decreased [Ca2+]i
into SR via SR Ca2+ATPase (SERCA, 70%) - Ca in SR for next contraction;
uptake of Ca in mitochondria
fancy name for contractility
inotropy
drugs used to correct acute or chronic heart failure do what to the heart
increase its contractility
how do drugs increase contractility
increase [Ca2+]i levels
how do heart failure drugs increase contractility/[Ca2+]i levels
increase VDCC activity OR
reduce Ca2+ extrusion
what classes of drug increase VDCC activity
sympathetic mimetic
what classes of drug reduce Ca2+ extrusion
cardiac glycosidases
how does beta 1 adrenoceptor stimulation a contractility increase
NA binds B1 > Gs, AC, inc cAMP inc PKA, inc Pi'n of VDCCs inc Ca influx, inc CICR inc sliding filament mechanism inc contractility
effect of increased PKA on force of contraction
increased Ca2+ influx
increased FOC
effect of increased PKA
increased open K channels increased repolarisation inc SERCA activity increased Ca uptake both increase relaxation
sympathetic effect on inotropy
positive - increased contractility
sympathetic effect on chrontropy
positive - increased HR
Sympathetic effect on dromotropy
positive - increased conduction through AV node
sympathetic effect on relaxation
positive lusitropic effect - increase rate of relaxation, K channels, SERCA
what are drugs that have positive inotropic action called
inotropes
examples of inotropes
cardiac glyocsidases
how does digoxin work
reducing Ca2+ extrusion
what does digoxin do
increase contractility
what is the mechanism of action for digoxin
inhibits Na+/K+ ATPase
causing [Na+]i build up
less Ca2+ extrusion by NCX
More Ca uptake by stores, therefore greater CICR
what do dobutamine and dopamine act on
beta one adrenoceptors - may be used in acute heart failure
where does glucagon act
acts on Gs coupled receptor - increase cAMP and PKA activity - used in patients with acute heart failure that take B blockers
what is amrinone
a phosphodiesterase inhibitor (PDE)
which PDE is heart specific
Type 3/PDE3
how does PDE reduce cAMP
by converting cAMP to AMP
what is the result of PDE’s conversion of cAMP to AMP
reduction in cAMP, reduced activity of PKA
what is the IC result of PDE inhibition
cAMP build up - PKA activated to increase activity of VDCCs and increased Ca2+ - only used in transplant cases
what is the link between electrical activity, change in [Ca2+]i, and contraction
higher activation of VDCCs
higher Ca2+ influx
stronger force of contraction
what causes a rise and a reduction in [Ca2+]i in cardiac myocytes
u
what is the importance of a submaximal effect of [Ca2+]i in cardiac myocytes - how does this differ to skeletal muscle?
n
how does a rise in [Ca2+]i produce contraction?
fin
can you define the differences between inotropy and Starling’s law
i
Can you describe the effects of the SNS on the heart?
sh
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