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CV - regulation of the cardiovascular system Flashcards

1
Q

define G-protein coupled receptors (GPCRs)

A

7-transmembrane-spanning integral membrane proteins that transduce ligand binding to intracellular signalling

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2
Q

name a few of the many cardiovascular GPCRs (6)

A 
alpha-adrenergic receptors
beta-adrenergic receptors
acetylcholine receptors
endothelia receptors
adenosine receptors
angiotensin II receptors
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3
Q

what are the steps in the GPCR activation scheme?

A

agonist binds GPCR
GTP replaces GDP on the alpha subunit of the heterotrimeric G protein
GTP binding causes dissociation of the alpha and beta-gamma G protein subunits
both alpha and beta-gamma subunits may be active signals

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4
Q

what are the steps in GPCR deactivation?

A

autodephosphorylation of GTP to GDP by the alpha subunit
reassociation of the alpha and beta-gamma subunits
rebinding of the G protein to the receptor causing inactivation

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5
Q

what three families of GPCR are involved in cardiovascular function?

A

Gs, Gi/o, Gq

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6
Q

Gs is ____________ for cAMP production by adenylate cyclase.

A

stimulatory

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7
Q

Gs is stimulatory for ____________ production by adenylate cyclase.

A

cAMP

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8
Q

Gi/o is ____________ for cAMP production by adenylate cyclase.

A

inhibitory

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9
Q

Gi/o is inhibitory for ____________ production by adenylate cyclase.

A

cAMP

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10
Q

Gq activation increases ____________ via activation of phospholipase C (PLC) and protein kinase C (PKC).

A

intracellular Ca2+

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11
Q

Gq activation increases intracellular Ca2+ via activation of ____________ and ____________.

A 
phospholipase C (PLC)
protein kinase C (PKC)
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12
Q

what is the functional effect of alpha1 adrenergic receptor activation and Gq release?

A

vasoconstriction

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13
Q

what are the functional effects of beta-adrenergic receptor activation and Gs release in the heart? in the vascular system?

A

heart: increase chronotropy, inotropy, lusitropy, dromotropy

vascular beds in skeletal muscle: vasodilation

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14
Q

what are the functional effects of muscaneric acetylcholine receptors and Gi/o release?

A

decrease chronotropy

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15
Q

define chronotropy

A

firing of senatorial node, heart rate

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16
Q

define inotropy

A

contraction of myocardium, contractility

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17
Q

define lusitropy

A

relaxation of myocardium

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18
Q

define dromotropy

A

conduction velocity of the AV node

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19
Q

what is a chronotropic agent?

A

one that affects the heart rate

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20
Q

what is an inotropic agent?

A

one that affects the contractility of the heart, alters the force or energy of muscle contractions

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21
Q

what is a lusitropic agent?

A

one that affects the rate of myocardial relaxation

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22
Q

what is a dromotropic agent?

A

one that affects the conduction velocity of the AV node

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23
Q

describe the stimulation of cAMP production in the heart

A

sympathetic neurons innervate the heart and release norepinephrine, which binds to and activates beta adrenergic receptors to increase cAMP production

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24
Q

how are phosphodiesterases involved in the regulation of cAMP signaling in the heart?

A

phosphodiesterases breakdown cAMP and cGMP and help to establish intracellular signaling micro domains and specificity of cAMP signaling in the heart

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25
how is protein kinase A (PKA) involved in the regulation of cAMP signaling in the heart?
cAMP-dependent PKA is a major effector for cAMP signaling in the heart via phosphorylation of cAMP target proteins.
26
what are the molecular target for sympathetic regulation of inotropy and lusitropy?
``` phospholamban (PLB) L-type Ca2+ channels (LTCCs) ryanodine receptors (RyRs) troponin I (TnI) ```
27
what is the effect of phosphorylation of phospholamban (PLB) by PKA on Ca2+ levels in the cytosol of myocytes?
phosphorylation of PLB by PKA causes its dissociation from SERCA, thereby relieving inhibition of SERCA and increasing the Ca2+ reuptake rate (removal of Ca2+ from the cytosol), directly increasing lusitropy and inotropy
28
PLB is an ____________ of SERCA
inhibitor
29
phosphorylation of PLB by PKA causes it to ____________.
dissociate from SERCA
30
describe the action of SERCA
SERCA removes Ca2+ from the cytosol following contraction by pumping Ca2+ back into the sarcoplasmic reticulum
31
in what two ways does faster Ca2+ reuptake affect cardiac function?
1 directly increases lusitropy - the ability of the heart to relax 2 increases inotropy (contractility) by increasing SR Ca2+ load
32
L-type Ca2+ channels (LTCCs) on the plasma membrane are activated by ____________.
depolarization
33
what is triggered by the influx of Ca2+ through LTCCs?
larger Ca2+ release from the SR via RyRs, termed Ca2+-induced Ca2+ release (CICR)
34
what is the sequence of effects of phosphorylation of LTCCs by PKA?
phosphorylation of LTCCs by PKA slows inactivation, thereby increasing the magnitude of the LTCC current (I_Ca-L) and increasing the "trigger [Ca2+]" and eliciting a larger release of Ca2+ from the SR, thereby increasing inotropy
35
what is the net effect of phosphorylation of LTCCs by PKA?
increase in inotropy (contractility)
36
phosphorylation of RyRs by PKA ____________ their sensitivity to Ca2+.
increases
37
the increase in sensitivity of RyRs to Ca2+ by PKA phosphorylation decreases the "trigger [Ca2+]" needed to evoke Ca2+ release from the SR, thus ____________.
increasing inotropy
38
the net effect of phosphorylation of RyRs by PKA is ____________.
increase in inotropy (contractility)
39
troponin I is the ____________ unit of the troponin complex.
inhibitory
40
TnI inhibits the interaction between ____________ and ____________ in the absence of Ca2+.
actin | myosin
41
phosphorylation of TnI by PKA ____________ the Ca2+ sensitivity of TnC.
decreases
42
the net effects of TnI phosphorylation by PKA are ____________ and ____________.
decrease in inotropy | increase in lusitropy
43
what is the mechanism leading to the increase in lusitropy after decreased sensitivity of TnC to Ca2+?
decreased sensitivity of TnC to Ca2+ results in faster dissociation of Ca2+ from TnC, increasing lusitropy
44
increasing lusitropy causes the heart to fill more ____________.
quickly
45
describe the parasympathetic regulation of inotropy
parasympathetic innervation of the ventricle is sparse, thus there is little parasympathetic control of inotropy
46
the sympathetic nervous system is involved in the ____________ response.
fight-or-flight
47
the sympathetic nervous system innervates the ____________ and ____________.
heart | vasculature
48
the sympathetic nervous system increases ____________, ____________, ____________, and ____________.
``` heart rate (chronotropy) contractility (inotropy) conduction velocity (dromotropy) relaxation rate (lusitropy) ```
49
what is the general effect of the sympathetic nervous system on the vasculature?
causes general vasoconstriction
50
what is the main neurotransmitter of the sympathetic nervous system?
norepinephrine
51
on which receptors does norepinephrine act?
adrenergic receptors
52
the parasympathetic nervous system is involved in the ____________ response.
rest-and-digest
53
the parasympathetic nervous system innervates the ____________, ____________, and ____________, with limited innervation of the ____________.
sinoatrial node atrioventricular node conduction system of the heart ventricles
54
the parasympathetic nervous system ____________ heart rate with little direct effect on ____________.
decreases | contractility
55
there is relatively little parasympathetic innervation of ____________.
vasculature
56
what is the main neurotransmitter of the parasympathetic nervous system?
acetylcholine
57
on what receptors does acetylcholine act?
cholinergic
58
sympathetic stimulation ____________ inotropy.
increases
59
parasympathetic stimulation ____________ inotropy.
doesn't really effect
60
sympathetic stimulation ____________ chronotropy (heart rate).
increases
61
parasympathetic stimulation ____________ chronotropy (heart rate).
decreases
62
what are the molecular targets for sympathetic stimulation of chronotropy?
hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) L-type Ca++ channels (LTCCs) and RyRs RyRs and NCX
63
HCN channels produce which cardiac current?
cardiac funny current (I_f)
64
what is the cardiac funny current?
an inward (depolarizing) current at diastolic potential

CVPR (14 decks)

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