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CVPR Exam I > 9. Regulation of the CV System > Flashcards

9. Regulation of the CV System Flashcards

1
Q

What does CICR stand for?

A

Ca2+-induced Ca2+ release

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1
Q

Decreased sensitivity also results in faster dissociation of ____ from TnC, thereby increasing lusitropy, which allows the heart to fill more quickly.

A

Ca2+

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2
Q

Stretch of the arterial cell wall where the baroreceptors sit activates _____ to cause depolarization and to trigger an AP.

A

mechanosensitive eNac Na+ channels

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3
Q

What is dromotropy?

A

affects the conduction speed of the AV node

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3
Q

Phosphorylation of ____ decreases the Ca2+ sensitivity of TnC.

A

TnI

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4
Q

What is the HCN channel?

A

the channel that produces the funny current (If)

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4
Q

If the net current is inward, it is _____.

A

depolarizing

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4
Q

Where are baroreceptors located?

A

in the aortic arch and carotid sinus

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5
Q

Block of _____ receptors with atropine increases heart rate by inhibiting tonic parasympathetic activity.

A

M2 muscarinic acetylcholine

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5
Q

Block of β adrenergic receptors with propanolol _____ by inhibiting tonic sympathetic activity.

A

decreases heart rate

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5
Q
  • Ca++ channel - phosphorylation by PKA slows inactivation, increases Ca++ - increases ionotropy
A

L-type Ca++ channel (DHPR)

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7
Q

What produces cAMP?

A

adenylate cyclase

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8
Q

What is lusitropy?

A

myocardial/diastolic relaxation (the ability of the heart to relax)

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9
Q

In vascular smooth muscle cells, adenosine binds to _____.

A

A2 purinergic receptors

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10
Q

PKA also phosphorylates ____, making them more sensitive to Ca2+, so that less trigger Ca2+ is needed to evoke Ca2+ release.

A

ryanodine receptors

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10
Q

What is phospholambam?

A
  • protein that PKA phosphorylates to remove - inhibits SERCA; remove for faster Ca++ into SR - increases inotropy and lusitropy - part of EC coupling
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11
Q

Parasympathetic Regulation of Chronotropy: ACh binds to the M2 muscarinic ACh receptor, activating Gi and inhibiting AdCy. The Beta-gamma subunits bind to ____ channel, which are K+ channels, causing _____ and decreased excitability of the cell to ____ the heart rate.

A

hyperpolarization; slow

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12
Q

The influx of Ca2+ through L-type Ca2+ channels triggers a larger Ca2+ release from the ___ via ryanodine receptors, a process termed Ca2+-induced Ca2+ release (CICR).

A

SR

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13
Q

What is an increase in HR in response to stretch called?

A

the Bainbridge Reflex

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14
Q

Name 3 ways the CNS controls the vasculature.

A
  1. sympathetic regulation 2. baroreceptor reflex 3. CNS control center
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15
Q

Block of _____ receptors with propanolol decreases heart rate by inhibiting tonic sympathetic activity.

A

β adrenergic

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16
Q

What are GPCRs?

A

7-transmembrane-spanning (7TM) integral membrane proteins that transduce ligand binding to intracellular signaling

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16
Q

What is the Bainbridge Reflex?

A

an increase in HR in response to stretch

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17
Q

How does a GPCR get activated?

A
  1. agonist binds receptor 2. GTP replaces GDP on α-subunit of heterotrimeric G protein 3. dissociation of α and βγ G protein subunits
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17
Q

____ also phosphorylates ryanodine receptors, making them more sensitive to Ca2+, so that less trigger Ca2+ is needed to evoke Ca2+ release.

A

PKA

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18
Q

Decreased sensitivity also results in faster dissociation of Ca2+ from TnC, thereby increasing ____, which allows the heart to fill more quickly.

A

lusitropy

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19
Q

Faster Ca2+ reuptake has two effects on cardiac performance: 1) directly increases ____ and 2) increases inotropy by increasing SR Ca2+ load.

A

lusitropy

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19
Q

How is MLCK dephosphorylated?

A

by myosin light chain phosphatase (MLCP)

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19
Q

Low pressure baroreceptors in the atria and vena cavae mediate the ______.

A

Bainbridge Reflex

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21
Q

Name 3 families of G proteins involved in CV system function.

A
  1. Gs 2. Gi/o 3. Gq
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22
Q

How is cAMP’s role different in cardiac muscle vs smooth muscle?

A

in smooth muscle, cAMP causes relaxation

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23
Q

What is a Ryanodine Receptors (RyRs)?

A
  • an intracellular calcium receptor - mediates Ca++ release from the SR (CICR) - a molecular target for sympathetic regulation of ino- and lustropy - its phosphorylation increases Ca++ sensiivity
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24
Q

Block of M2 muscarinic acetylcholine receptors with atropine _____ by inhibiting tonic parasympathetic activity.

A

increases heart rate

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24
Q

Where is the L-type Ca++ channel (DHPR) located?

A

on the T-tubule

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24
Q

In vascular smooth muscle cells, ____ binds to A2 purinergic receptors.

A

adenosine

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25
Q

Parasympathetic Regulation of Chronotropy: ACh binds to the M2 muscarinic ACh receptor, activating Gi and inhibiting AdCy. The Beta-gamma subunits bind to the GIRK channel, which are _____ channels, causing hyperpolarization and decreased excitability of the cell to slow the heart rate.

A

K+

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26
Q

What is the effect of muscarinic ACh receptor binding?

A

decrease chronotropy

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27
Q

L-type Ca2+ channels on the plasma membrane are activated by _____.

A

depolarization

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28
Q

Sympathetic Regulation of Chronotropy: NE binds to the Beta-adrenergic receptor, activating Gs and AdCy. The cAMP produced can then activate PKA, which then phosphorylates _____ or _____.

A

the L-type Ca++ channel or the RyR2

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29
Q

What does the brain do in response to baroreceptor firing?

A

slow heart rate and vasodilate BVs in an effort to decrease the BP

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30
Q

____ are the most prevalent drug target.

A

GPCRs

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30
Q

How are smooth muscle cells different than striated muscle?

A
  1. they’re small and mononucleate 2. no sarcomeres 3. no striations 4. no troponin or tropomyosin 5. don’t require Ca++ release from SR 6. slower rate of contraction but can sustain it
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30
Q

Stretch of the arterial cell wall where the baroreceptors sit activates mechanosensitive eNac Na+ channels to cause _____ and to trigger _____.

A

depolarization; an AP

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31
Q

What does MLCP stand for?

A

myosin light chain phosphatase

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32
Q
  • an intracellular calcium receptor - mediates Ca++ release from the SR (CICR) - a molecular target for sympathetic regulation of ino- and lustropy - its phosphorylation by PKA increases Ca++ sensiivity
A

RyR2

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34
Q

SERCA removes ____ from cytosol following contraction (pumps it back into the _____).

A

Ca2+; sarcoplasmic reticulum (SR)

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34
Q

What is inotropy?

A

contractility

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36
Q

Name some of the CV GPCRs.

A

α & β adrenergic receptors, acetylcholine receptors, endothelin receptors, adenosine receptors, angiotensin II receptors

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37
Q

Sympathetic Regulation of Chronotropy: NE binds to the Beta-adrenergic receptor, activating Gs and AdCy. The cAMP produced can then directly act upon?

A

the HCN channel

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38
Q

What is troponin-I (TnI)?

A
  • sarcomeric protein - phosphorylation by PKA decreases sensitivity Ca++ sensitivity of troponin-C - allows faster dissociation of Ca++ so faster filling = increased lusitropy
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39
Q

Parasympathetic Regulation of Chronotropy: ACh binds to the M2 muscarinic ACh receptor, activating Gi and inhibiting AdCy. The Beta-gamma subunits bind to the ____ channel, which are K+ channels, causing hyperpolarization and decreased excitability of the cell to slow the heart rate.

A

GIRK

41
Q

Along with ____, TnI inhibits the interaction between actin and myosin in the absence of Ca2+.

A

tropomyosin

43
Q

Name 4 molecular targets for sympathetic regulation of inotropy and lusitropy.

A
  1. Phospholamban (PLB) 2. L-type Ca2+ channels (LTCCs) 3. Ryanodine Receptors (RyRs) 4. Troponin I (TnI)
44
Q

What is inotropy?

A

strength of muscle contraction

46
Q

PLB is an inhibitor of ____.

A

SERCA

48
Q

What do Beta-blockers treat?

A

arrhythmias, hypertension, cardioprotection post-MI

49
Q

What does myosin light chain phosphatase (MLCP) do?

A

dephosphorylates MLCK to stop smooth muscle contraction

50
Q

Along with tropomyosin, TnI inhibits the interaction between ____ and ____ in the absence of Ca2+.

A

actin; myosin

50
Q

Phosphorylation of TnI decreases the ____ of TnC.

A

Ca2+ sensitivity

50
Q

The baroreceptor cell axons project to the ____ of the brain via the glossopharyngeal nerve or the vagus nerve.

A

cardiovascular control center in the medulla

50
Q

The baroreceptor cell axons project to the cardiovascular control center in the medulla of the brain via the _____ nerve or the _____ nerve.

A

glossopharyngeal; vagus

51
Q

How is a GPCR deactivated?

A

GTP dephosphorylated to GDP

52
Q

What is the L-type Ca++ channel (DHPR)?

A
  • Ca++ channel - phosphorylation by PKA slows inactivation, increases Ca++ - increases ionotropy
52
Q

Adenosine increases ____ levels in VSMCs causing vasodilation by inhibition of myosin light chain kinase.

A

cAMP

54
Q

What is chronotropy?

A

heart rate

55
Q

A metabolically active tissue produces ______ that regulate arterial resistance and thereby blood flow.

A

vasoactive metabolites

55
Q

Name some vasoactive metabolites.

A

adenosine, PO4-, K+, H+, CO2, lactate; decreased PO2

55
Q

_____ increases cAMP levels in VSMCs causing vasodilation by inhibition of myosin light chain kinase.

A

Adenosine

56
Q

What is the 1a way blood flow in the capillaries is modified to match demand?

A

vasoactive metabolites

57
Q

___ is an inhibitor of SERCA.

A

PLB

58
Q

______ where the baroreceptors sit activates _____ to cause depolarization and to trigger an AP.

A

Stretch of the arterial cell wall

60
Q

What is the PNS?

A

rest and digest

61
Q

Sympathetic stimulation = _____ (usually)

A

vasoconstriction

62
Q

_____ is produced by hydrolysis of ATP and is an important vasoactive metabolite.

A

Adenosine

64
Q

Block of β adrenergic receptors with ____ decreases heart rate by inhibiting tonic sympathetic activity.

A

propanolol

65
Q

What molecule inhibits myosin light chain kinase (MLCK) to cause smooth muscle cell relaxation?

A

cAMP via PKA

66
Q

Inhibition of inward currents _____ and _____.

A

hyperpolarizes the cell; decreases excitability

68
Q

How does the PNS regulate inotropy?

A

it does very little to regulate- mostly SNS control

69
Q
  1. Ca++ enters cytoplasm from SR or plasma membrane channels 2. Ca++ binds calmodulin (CaM) 3. Ca++/CaM binds to Myosin Light Chain Kinase (MLCK) to activate it 4. MLCK phosphorylates the myosin head to allow cross bridge formation and cycling
A

steps in smooth muscle contraction

70
Q

Adenosine increases cAMP levels in VSMCs causing _____ by inhibition of myosin light chain kinase.

A

vasodilation

72
Q

Gq activation increases intracellular ____ via activation of phospholipase C (PLC) and Protein Kinase C (PKC).

A

Ca2+

73
Q

The influx of Ca2+ through _____ triggers a larger Ca2+ release from the SR via ryanodine receptors, a process termed Ca2+-induced Ca2+ release (CICR).

A

L-type Ca2+ channels

74
Q

Name 4 ways arterial pressure can be regulated.

A
  1. vascular smooth muscle contraction 2. neural control of the smooth muscle 3. intrinsic control of the vasculature 4. humoral control of the vasculature
76
Q

What is the effect of α1 adrenergic receptor binding?

A

vasoconstriction

78
Q

What is the SNS?

A

fight or flight

79
Q

The troponin complex consists of ____, ____, and ____.

A

TnC, TnI, and TnT

79
Q

What does MLCK stand for? What is this molecule a part of?

A

myosin light chain kinase; smooth muscle contraction

81
Q

α & β adrenergic receptors, acetylcholine receptors, endothelin receptors, adenosine receptors, and angiotensin II receptors are all?

A

cardiovascular GPCRs

83
Q

SNS stimulation increases _____.

A

inotropy

84
Q
  • sarcomeric protein - phosphorylation by PKA decreases sensitivity Ca++ sensitivity of troponin-C - allows faster dissociation of Ca++ so faster filling = increased lusitropy
A

troponin-I (TnI)

86
Q

What do angiotensin II receptor blockers treat?

A

HTN, heart failure

87
Q

What G protein does the α1 adrenergic receptor use?

A

Gq

88
Q

What is the baroreceptor reflex?

A

a short term and rapid negative feedback mechanism for sudden changes in BP

89
Q

Faster ____ reuptake has two effects on cardiac performance: 1) directly increases “lusitropy” and 2) increases inotropy by increasing SR Ca2+ load.

A

Ca2+

91
Q

Gs is _____ while Gi is _____ for cAMP production.

A

stimulatory, inhibitory

91
Q

Parasympathetic Regulation of Chronotropy: ACh binds to the M2 muscarinic ACh receptor, activating Gi and inhibiting AdCy. The cAMP production is also inhibited, thereby decreasing activity of the _____, the _____, the ____, and the _____.

A

HCN channel; L-type Ca++ channel; RyR2; NCX

92
Q

_____ is the inhibitory unit of the troponin complex.

A

Troponin I

93
Q

List the steps in smooth muscle contraction.

A
  1. Ca++ enters cytoplasm from SR or plasma membrane channels 2. Ca++ binds calmodulin (CaM) 3. Ca++/CaM binds to Myosin Light Chain Kinase (MLCK) to activate it 4. MLCK phosphorylates the myosin head to allow cross bridge formation and cycling
94
Q

What are baroreceptors made of?

A

pressure-sensitive neurons

95
Q

What is the effect of β adrenergic receptor binding?

A

heart: increase chronotropy, inotropy, lusitropy, dromotropy vascular beds in skeletal muscle: vasodilation

96
Q

Faster Ca2+ reuptake has two effects on cardiac performance: 1) directly increases “lusitropy” and 2) increases ____ by ____.

A

inotropy; increasing SR Ca2+ load

98
Q

_____ removes Ca2+ from cytosol following contraction (pumps it back into the sarcoplasmic reticulum (SR)).

A

SERCA

99
Q

If the net current is _____, it is depolarizing.

A

inward

100
Q

What is a 7-transmembrane-spanning (7TM) integral membrane proteins that transduce ligand binding to intracellular signaling called?

A

a GPCR

102
Q

The ____ nervous system is fight or flight; the ____ nervous system is rest and digest.

A

sympathetic; parasympathetic

103
Q

Since APs are not required to trigger contraction in a smooth muscle cells, what does trigger it?

A

mechanical, chemical, or electrical stimuli

104
Q

Gq activation increases intracellular Ca2+ via activation of ____ and _____.

A

phospholipase C (PLC); Protein Kinase C (PKC)

106
Q

In the NCX, for every ____ molecule of Ca++ pushed out, ____ molecule of Na is brought in.

A

1; 3

107
Q

In the NCX, for every 1 molecule of ____ pushed out, 3 molecules of ____ is brought in.

A

Ca++; Na

109
Q

What stops smooth muscle contraction?

A

dephosphorylation of MLCK by MLCP

110
Q

What G protein does the muscarinic ACh receptor use?

A

Gi/o

111
Q

Decreased sensitivity also results in faster dissociation of Ca2+ from ____, thereby increasing lusitropy, which allows the heart to fill more quickly.

A

TnC

112
Q

What G protein does the β adrenergic receptor use?

A

Gs

113
Q

_____ nervous system stimulation increases inotropy.

A

Sympathetic

114
Q

____ activation increases intracellular Ca2+ via activation of phospholipase C (PLC) and Protein Kinase C (PKC).

A

Gq

115
Q

____ is the inhibitory unit of the troponin complex.

A

Troponin I (TnI)

116
Q

Name the 3 major CV ANS signaling pathways.

A
  1. α1 adrenergic 2. β adrenergic 3. muscarinic ACh
118
Q
  1. they’re small and mononucleate 2. no sarcomeres 3. no striations 4. no troponin or tropomyosin 5. don’t require Ca++ release from SR 6. slower rate of contraction but can sustain it
A

smooth muscle cells

119
Q

Phosphorylation of TnI decreases the Ca2+ sensitivity of ___.

A

TnC

120
Q

The influx of Ca2+ through L-type Ca2+ channels triggers a larger Ca2+ release from the SR via ____ a process termed Ca2+-induced Ca2+ release (CICR).

A

ryanodine receptors

121
Q

Block of M2 muscarinic acetylcholine receptors with _____ increases heart rate by inhibiting tonic parasympathetic activity.

A

atropine

122
Q

Sympathetic Regulation of Chronotropy: NE binds to the Beta-adrenergic receptor, activating Gs and AdCy. The cAMP produced can then activate PKA, which then phosphorylates the L-type Ca++ channel or the RyR2. These release Ca++ which can then be pumped out of the cell while Na is simultaneously brought in, via the _____.

A

NCX

123
Q

Sympathetic stimulation directly activates VSMC contraction independent of ____.

A

membrane depolarization

124
Q
  • protein that PKA phosphorylates - uninhibits SERCA for faster Ca++ into SR - increases inotropy and lusitropy - part of EC coupling
A

phospholambam

125
Q

What is the 1a parasympathetic mechanism of slowing the heart rate?

A

activation of the I kach current via the GIRK channel

CVPR Exam I (29 decks)

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