9. Regulation of the CV System Flashcards
What does CICR stand for?
Ca2+-induced Ca2+ release
Decreased sensitivity also results in faster dissociation of ____ from TnC, thereby increasing lusitropy, which allows the heart to fill more quickly.
Ca2+
Stretch of the arterial cell wall where the baroreceptors sit activates _____ to cause depolarization and to trigger an AP.
mechanosensitive eNac Na+ channels
What is dromotropy?
affects the conduction speed of the AV node
Phosphorylation of ____ decreases the Ca2+ sensitivity of TnC.
TnI
What is the HCN channel?
the channel that produces the funny current (If)
If the net current is inward, it is _____.
depolarizing
Where are baroreceptors located?
in the aortic arch and carotid sinus
Block of _____ receptors with atropine increases heart rate by inhibiting tonic parasympathetic activity.
M2 muscarinic acetylcholine
Block of β adrenergic receptors with propanolol _____ by inhibiting tonic sympathetic activity.
decreases heart rate
- Ca++ channel - phosphorylation by PKA slows inactivation, increases Ca++ - increases ionotropy
L-type Ca++ channel (DHPR)
What produces cAMP?
adenylate cyclase
What is lusitropy?
myocardial/diastolic relaxation (the ability of the heart to relax)
In vascular smooth muscle cells, adenosine binds to _____.
A2 purinergic receptors
PKA also phosphorylates ____, making them more sensitive to Ca2+, so that less trigger Ca2+ is needed to evoke Ca2+ release.
ryanodine receptors
What is phospholambam?
- protein that PKA phosphorylates to remove - inhibits SERCA; remove for faster Ca++ into SR - increases inotropy and lusitropy - part of EC coupling
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.
hyperpolarization; slow
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).
SR
What is an increase in HR in response to stretch called?
the Bainbridge Reflex
Name 3 ways the CNS controls the vasculature.
- sympathetic regulation 2. baroreceptor reflex 3. CNS control center
Block of _____ receptors with propanolol decreases heart rate by inhibiting tonic sympathetic activity.
β adrenergic
What are GPCRs?
7-transmembrane-spanning (7TM) integral membrane proteins that transduce ligand binding to intracellular signaling
What is the Bainbridge Reflex?
an increase in HR in response to stretch
How does a GPCR get activated?
- agonist binds receptor 2. GTP replaces GDP on α-subunit of heterotrimeric G protein 3. dissociation of α and βγ G protein subunits
____ also phosphorylates ryanodine receptors, making them more sensitive to Ca2+, so that less trigger Ca2+ is needed to evoke Ca2+ release.
PKA
Decreased sensitivity also results in faster dissociation of Ca2+ from TnC, thereby increasing ____, which allows the heart to fill more quickly.
lusitropy
Faster Ca2+ reuptake has two effects on cardiac performance: 1) directly increases ____ and 2) increases inotropy by increasing SR Ca2+ load.
lusitropy
How is MLCK dephosphorylated?
by myosin light chain phosphatase (MLCP)
Low pressure baroreceptors in the atria and vena cavae mediate the ______.
Bainbridge Reflex
Name 3 families of G proteins involved in CV system function.
- Gs 2. Gi/o 3. Gq
How is cAMP’s role different in cardiac muscle vs smooth muscle?
in smooth muscle, cAMP causes relaxation
What is a Ryanodine Receptors (RyRs)?
- 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
Block of M2 muscarinic acetylcholine receptors with atropine _____ by inhibiting tonic parasympathetic activity.
increases heart rate
Where is the L-type Ca++ channel (DHPR) located?
on the T-tubule
In vascular smooth muscle cells, ____ binds to A2 purinergic receptors.
adenosine
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.
K+
What is the effect of muscarinic ACh receptor binding?
decrease chronotropy
L-type Ca2+ channels on the plasma membrane are activated by _____.
depolarization
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 _____.
the L-type Ca++ channel or the RyR2
What does the brain do in response to baroreceptor firing?
slow heart rate and vasodilate BVs in an effort to decrease the BP
____ are the most prevalent drug target.
GPCRs
How are smooth muscle cells different than striated muscle?
- 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
Stretch of the arterial cell wall where the baroreceptors sit activates mechanosensitive eNac Na+ channels to cause _____ and to trigger _____.
depolarization; an AP
What does MLCP stand for?
myosin light chain phosphatase
- 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
RyR2
SERCA removes ____ from cytosol following contraction (pumps it back into the _____).
Ca2+; sarcoplasmic reticulum (SR)
What is inotropy?
contractility
Name some of the CV GPCRs.
α & β adrenergic receptors, acetylcholine receptors, endothelin receptors, adenosine receptors, angiotensin II receptors
Sympathetic Regulation of Chronotropy: NE binds to the Beta-adrenergic receptor, activating Gs and AdCy. The cAMP produced can then directly act upon?
the HCN channel
What is troponin-I (TnI)?
- sarcomeric protein - phosphorylation by PKA decreases sensitivity Ca++ sensitivity of troponin-C - allows faster dissociation of Ca++ so faster filling = increased lusitropy
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.
GIRK
Along with ____, TnI inhibits the interaction between actin and myosin in the absence of Ca2+.
tropomyosin
Name 4 molecular targets for sympathetic regulation of inotropy and lusitropy.
- Phospholamban (PLB) 2. L-type Ca2+ channels (LTCCs) 3. Ryanodine Receptors (RyRs) 4. Troponin I (TnI)
What is inotropy?
strength of muscle contraction
PLB is an inhibitor of ____.
SERCA
What do Beta-blockers treat?
arrhythmias, hypertension, cardioprotection post-MI
What does myosin light chain phosphatase (MLCP) do?
dephosphorylates MLCK to stop smooth muscle contraction
Along with tropomyosin, TnI inhibits the interaction between ____ and ____ in the absence of Ca2+.
actin; myosin
Phosphorylation of TnI decreases the ____ of TnC.
Ca2+ sensitivity
The baroreceptor cell axons project to the ____ of the brain via the glossopharyngeal nerve or the vagus nerve.
cardiovascular control center in the medulla
The baroreceptor cell axons project to the cardiovascular control center in the medulla of the brain via the _____ nerve or the _____ nerve.
glossopharyngeal; vagus
How is a GPCR deactivated?
GTP dephosphorylated to GDP
What is the L-type Ca++ channel (DHPR)?
- Ca++ channel - phosphorylation by PKA slows inactivation, increases Ca++ - increases ionotropy
Adenosine increases ____ levels in VSMCs causing vasodilation by inhibition of myosin light chain kinase.
cAMP
What is chronotropy?
heart rate
A metabolically active tissue produces ______ that regulate arterial resistance and thereby blood flow.
vasoactive metabolites
Name some vasoactive metabolites.
adenosine, PO4-, K+, H+, CO2, lactate; decreased PO2
_____ increases cAMP levels in VSMCs causing vasodilation by inhibition of myosin light chain kinase.
Adenosine
What is the 1a way blood flow in the capillaries is modified to match demand?
vasoactive metabolites
___ is an inhibitor of SERCA.
PLB
______ where the baroreceptors sit activates _____ to cause depolarization and to trigger an AP.
Stretch of the arterial cell wall
What is the PNS?
rest and digest
Sympathetic stimulation = _____ (usually)
vasoconstriction
_____ is produced by hydrolysis of ATP and is an important vasoactive metabolite.
Adenosine
Block of β adrenergic receptors with ____ decreases heart rate by inhibiting tonic sympathetic activity.
propanolol
What molecule inhibits myosin light chain kinase (MLCK) to cause smooth muscle cell relaxation?
cAMP via PKA
Inhibition of inward currents _____ and _____.
hyperpolarizes the cell; decreases excitability
How does the PNS regulate inotropy?
it does very little to regulate- mostly SNS control
- 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
steps in smooth muscle contraction
Adenosine increases cAMP levels in VSMCs causing _____ by inhibition of myosin light chain kinase.
vasodilation
Gq activation increases intracellular ____ via activation of phospholipase C (PLC) and Protein Kinase C (PKC).
Ca2+
The influx of Ca2+ through _____ triggers a larger Ca2+ release from the SR via ryanodine receptors, a process termed Ca2+-induced Ca2+ release (CICR).
L-type Ca2+ channels
Name 4 ways arterial pressure can be regulated.
- vascular smooth muscle contraction 2. neural control of the smooth muscle 3. intrinsic control of the vasculature 4. humoral control of the vasculature
What is the effect of α1 adrenergic receptor binding?
vasoconstriction
What is the SNS?
fight or flight
The troponin complex consists of ____, ____, and ____.
TnC, TnI, and TnT
What does MLCK stand for? What is this molecule a part of?
myosin light chain kinase; smooth muscle contraction
α & β adrenergic receptors, acetylcholine receptors, endothelin receptors, adenosine receptors, and angiotensin II receptors are all?
cardiovascular GPCRs
SNS stimulation increases _____.
inotropy
- sarcomeric protein - phosphorylation by PKA decreases sensitivity Ca++ sensitivity of troponin-C - allows faster dissociation of Ca++ so faster filling = increased lusitropy
troponin-I (TnI)
What do angiotensin II receptor blockers treat?
HTN, heart failure
What G protein does the α1 adrenergic receptor use?
Gq
What is the baroreceptor reflex?
a short term and rapid negative feedback mechanism for sudden changes in BP
Faster ____ reuptake has two effects on cardiac performance: 1) directly increases “lusitropy” and 2) increases inotropy by increasing SR Ca2+ load.
Ca2+
Gs is _____ while Gi is _____ for cAMP production.
stimulatory, inhibitory
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 _____.
HCN channel; L-type Ca++ channel; RyR2; NCX
_____ is the inhibitory unit of the troponin complex.
Troponin I
List the steps in smooth muscle contraction.
- 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
What are baroreceptors made of?
pressure-sensitive neurons
What is the effect of β adrenergic receptor binding?
heart: increase chronotropy, inotropy, lusitropy, dromotropy vascular beds in skeletal muscle: vasodilation
Faster Ca2+ reuptake has two effects on cardiac performance: 1) directly increases “lusitropy” and 2) increases ____ by ____.
inotropy; increasing SR Ca2+ load
_____ removes Ca2+ from cytosol following contraction (pumps it back into the sarcoplasmic reticulum (SR)).
SERCA
If the net current is _____, it is depolarizing.
inward
What is a 7-transmembrane-spanning (7TM) integral membrane proteins that transduce ligand binding to intracellular signaling called?
a GPCR
The ____ nervous system is fight or flight; the ____ nervous system is rest and digest.
sympathetic; parasympathetic
Since APs are not required to trigger contraction in a smooth muscle cells, what does trigger it?
mechanical, chemical, or electrical stimuli
Gq activation increases intracellular Ca2+ via activation of ____ and _____.
phospholipase C (PLC); Protein Kinase C (PKC)
In the NCX, for every ____ molecule of Ca++ pushed out, ____ molecule of Na is brought in.
1; 3
In the NCX, for every 1 molecule of ____ pushed out, 3 molecules of ____ is brought in.
Ca++; Na
What stops smooth muscle contraction?
dephosphorylation of MLCK by MLCP
What G protein does the muscarinic ACh receptor use?
Gi/o
Decreased sensitivity also results in faster dissociation of Ca2+ from ____, thereby increasing lusitropy, which allows the heart to fill more quickly.
TnC
What G protein does the β adrenergic receptor use?
Gs
_____ nervous system stimulation increases inotropy.
Sympathetic
____ activation increases intracellular Ca2+ via activation of phospholipase C (PLC) and Protein Kinase C (PKC).
Gq
____ is the inhibitory unit of the troponin complex.
Troponin I (TnI)
Name the 3 major CV ANS signaling pathways.
- α1 adrenergic 2. β adrenergic 3. muscarinic ACh
- 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
smooth muscle cells
Phosphorylation of TnI decreases the Ca2+ sensitivity of ___.
TnC
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).
ryanodine receptors
Block of M2 muscarinic acetylcholine receptors with _____ increases heart rate by inhibiting tonic parasympathetic activity.
atropine
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 _____.
NCX
Sympathetic stimulation directly activates VSMC contraction independent of ____.
membrane depolarization
- protein that PKA phosphorylates - uninhibits SERCA for faster Ca++ into SR - increases inotropy and lusitropy - part of EC coupling
phospholambam
What is the 1a parasympathetic mechanism of slowing the heart rate?
activation of the I kach current via the GIRK channel
