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CVPR > CV - regulation of the cardiovascular system > Flashcards

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
Q

how is protein kinase A (PKA) involved in the regulation of cAMP signaling in the heart?

A

cAMP-dependent PKA is a major effector for cAMP signaling in the heart via phosphorylation of cAMP target proteins.

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26
Q

what are the molecular target for sympathetic regulation of inotropy and lusitropy?

A 
phospholamban (PLB)
L-type Ca2+ channels (LTCCs)
ryanodine receptors (RyRs)
troponin I (TnI)
27
Q

what is the effect of phosphorylation of phospholamban (PLB) by PKA on Ca2+ levels in the cytosol of myocytes?

A

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
Q

PLB is an ____________ of SERCA

A

inhibitor

29
Q

phosphorylation of PLB by PKA causes it to ____________.

A

dissociate from SERCA

30
Q

describe the action of SERCA

A

SERCA removes Ca2+ from the cytosol following contraction by pumping Ca2+ back into the sarcoplasmic reticulum

31
Q

in what two ways does faster Ca2+ reuptake affect cardiac function?

A

1 directly increases lusitropy - the ability of the heart to relax
2 increases inotropy (contractility) by increasing SR Ca2+ load

32
Q

L-type Ca2+ channels (LTCCs) on the plasma membrane are activated by ____________.

A

depolarization

33
Q

what is triggered by the influx of Ca2+ through LTCCs?

A

larger Ca2+ release from the SR via RyRs, termed Ca2+-induced Ca2+ release (CICR)

34
Q

what is the sequence of effects of phosphorylation of LTCCs by PKA?

A

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
Q

what is the net effect of phosphorylation of LTCCs by PKA?

A

increase in inotropy (contractility)

36
Q

phosphorylation of RyRs by PKA ____________ their sensitivity to Ca2+.

A

increases

37
Q

the increase in sensitivity of RyRs to Ca2+ by PKA phosphorylation decreases the “trigger [Ca2+]” needed to evoke Ca2+ release from the SR, thus ____________.

A

increasing inotropy

38
Q

the net effect of phosphorylation of RyRs by PKA is ____________.

A

increase in inotropy (contractility)

39
Q

troponin I is the ____________ unit of the troponin complex.

A

inhibitory

40
Q

TnI inhibits the interaction between ____________ and ____________ in the absence of Ca2+.

A

actin

myosin

41
Q

phosphorylation of TnI by PKA ____________ the Ca2+ sensitivity of TnC.

A

decreases

42
Q

the net effects of TnI phosphorylation by PKA are ____________ and ____________.

A

decrease in inotropy

increase in lusitropy

43
Q

what is the mechanism leading to the increase in lusitropy after decreased sensitivity of TnC to Ca2+?

A

decreased sensitivity of TnC to Ca2+ results in faster dissociation of Ca2+ from TnC, increasing lusitropy

44
Q

increasing lusitropy causes the heart to fill more ____________.

A

quickly

45
Q

describe the parasympathetic regulation of inotropy

A

parasympathetic innervation of the ventricle is sparse, thus there is little parasympathetic control of inotropy

46
Q

the sympathetic nervous system is involved in the ____________ response.

A

fight-or-flight

47
Q

the sympathetic nervous system innervates the ____________ and ____________.

A

heart

vasculature

48
Q

the sympathetic nervous system increases ____________, ____________, ____________, and ____________.

A 
heart rate (chronotropy)
contractility (inotropy)
conduction velocity (dromotropy)
relaxation rate (lusitropy)
49
Q

what is the general effect of the sympathetic nervous system on the vasculature?

A

causes general vasoconstriction

50
Q

what is the main neurotransmitter of the sympathetic nervous system?

A

norepinephrine

51
Q

on which receptors does norepinephrine act?

A

adrenergic receptors

52
Q

the parasympathetic nervous system is involved in the ____________ response.

A

rest-and-digest

53
Q

the parasympathetic nervous system innervates the ____________, ____________, and ____________, with limited innervation of the ____________.

A

sinoatrial node
atrioventricular node
conduction system of the heart
ventricles

54
Q

the parasympathetic nervous system ____________ heart rate with little direct effect on ____________.

A

decreases

contractility

55
Q

there is relatively little parasympathetic innervation of ____________.

A

vasculature

56
Q

what is the main neurotransmitter of the parasympathetic nervous system?

A

acetylcholine

57
Q

on what receptors does acetylcholine act?

A

cholinergic

58
Q

sympathetic stimulation ____________ inotropy.

A

increases

59
Q

parasympathetic stimulation ____________ inotropy.

A

doesn’t really effect

60
Q

sympathetic stimulation ____________ chronotropy (heart rate).

A

increases

61
Q

parasympathetic stimulation ____________ chronotropy (heart rate).

A

decreases

62
Q

what are the molecular targets for sympathetic stimulation of chronotropy?

A

hyperpolarization-activated cyclic nucleotide-gated channels (HCNs)
L-type Ca++ channels (LTCCs) and RyRs
RyRs and NCX

63
Q

HCN channels produce which cardiac current?

A

cardiac funny current (I_f)

64
Q

what is the cardiac funny current?

A

an inward (depolarizing) current at diastolic potential

CVPR (14 decks)

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