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SPR2015 > Regulation of CV system 1 > Flashcards

Regulation of CV system 1 Flashcards

1
Q

Mechanism of Norepinephrine action of Beta1-adrenergic receptors in the heart

A

1) norepinephrine binds beta1 receptor (GPCR)
2) replace GDP by GTP on alpha subunit of G protein
3) alpha and beta-gamma subunits dissociate
4) alpha subunit –> activate AC
5) incr CaMP –> activate HCN PKA –> PKA phosphorylate
6) beta-gamma bind and activ Ca2+ or G inward rect K+ (GIRK)
7) Auto-dephos of GTP to GDP allows reassembly of G protein

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2
Q

What are targets of PKA-mediated phosphorylation?

A

1) L-type Ca2+ channels
2) RyR receptors
3) phospholamban
4) troponin 1

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3
Q

normal function of L-type Ca2+ channels

A

activ by depol

influx of Ca2+ that triggers further Ca2+ release from SR via RyR

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4
Q

Phosphorylation of L type Ca2+ channels causes…

A

Slows inactivation of L-type Ca2+ channels

increases magnitude of current

INCREASED INOTROPY

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5
Q

Phosphorylation of RyR causes

A

more sensitive to Ca2+

less Ca2+ needed to evoke Ca2+ release

INCREASES INOTROPY

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6
Q

Normal function of PLB

A

inhibits SERCA

inhibits removal Ca2+ from cytosol after contraction

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7
Q

Phosphorylation of PLB causes…

A

Dissociate from SERCA

increased Ca2+ reuptake after contraction

INCREASED INOTROPY AND INCREASED LUSITROPY (INCREASED SR CA2+ LOAD)

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8
Q

Normal function of troponin 1

A

inhibits actin-myosin interaction in absence of Ca2+

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9
Q

Phosphorylation of troponin 1 causes

A

decreases Ca2+ sensitivity of Troponin C/complex

increases rate of dissociation of Ca2+ from Troponin C

INCREASES LUSITROPY

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10
Q

Difference between Vascular smooth muscle cells and cardiac myocytes

striation

A

1) Smooth muscle = not striated (NO SARCOMERES)

Cardiac muscle = striated

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11
Q

Difference between Vascular smooth muscle cells and cardiac myocytes

TROPONIN

A

Smooth muscle = calcium dependent phosphorylation of myosin

Cardiac muscle = troponin on actin binds Ca2+ and initiates contraction

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12
Q

Difference between Vascular smooth muscle cells and cardiac myocytes

calcium role

A

Smooth muscle = does not require calcium release from SR
_____
Calcium reuptake similar in both smooth and cardiac muscle

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13
Q

Difference between Vascular smooth muscle cells and cardiac myocytes

rate of contraction

A

Smooth muscle = slower contraction
requires mechanical/electrical/chemical stim

Cardiac muscle = neuronal input then electrical stimulus

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14
Q

Difference between Vascular smooth muscle cells and cardiac myocytes

role of cAMP

A

Smooth muscle = cAMP causes relaxation

Cardiac muscle = cAMP causes contraction

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15
Q

Difference between Vascular smooth muscle cells and cardiac myocytes

nucleated/gap junctions

A

both are mononucleated with gap junctions

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16
Q

Steps in Ca2+ regulation of vascular smooth muscle contraction (THICK FILAMENT REGULATION)

A
  1. Ca2+ enters the cytoplasm from the SR (primarily) and plasma membrane channels
  2. Ca2+ binds Calmodulin (CaM)
  3. Ca2+-CaM binds Myosin Light Chain Kinase (MLCK)
  4. MLCK phosphorylates myosin head = myosin light chain = MLC to create cross-bridge
  5. Contraction stopped when the myosin head dephosphorylated by Myosin Light Chain Phosphatase (MLCP)
    6) cAMP (via PKA) inhib MLCK –> relaxation
17
Q

What is the effect of sympathetic stimulation on vascular tone?

A

Sympathetic innervation causes vasoconstriction INDEPENDENT OF MEMBRANE DEPOL

18
Q

STeps in sympathetic regulation of smooth muscle contraction

A
  1. Norepinephrine binds a1-adrenergic receptor (some a2) on vascular smooth muscle cells
  2. Gq-alpha subunit of GPCR activ phospholipase C (PLC)
  3. PLC produces DAG and IP3
  4. IP3 activates IP3 receptors on the SR
  5. Activation of IP3 receptors causes Ca2+ release from L-type Ca2+ channels and the SR
  6. Increased intracellular Ca2+ levels cause contraction and vasoconstriction
19
Q

What are the arterial baroreceptors?

A

Neurons in aortic arch and carotid sinus that increase firing rate in response to incr arterial pressure and stretch of arterial walls

20
Q

Activation of basoreceptors causes…

A

SHORT TERM FOR SUDDEN CHANGE IN BLOOD PRESSURE

1) decr in sympathetic output
2) increase in parasympathetic output

DECREASE HR, INOTROPY
CAUSES VASODILATION

21
Q

Steps of Baroreceptor reflex arc

A
  1. Epithelial Na+ channels (eNaC) open in response to stretching of the vessel walls
  2. Na+ current –> depolarization and AP is fired
  3. AP propagate down neuron to the cardiovascular control center (CV center) in medulla of brainstem
  4. CV center integrates signals from the neurons and regulates the sympathetic and parasympathetic responses
  5. Acute, short-term decrease in blood pressure
22
Q

Gs

A

activ adenylate cyclase

incr cAMP
activ PKA

23
Q

Gi/Go

A

inhib AC

decr cAMP
inhib PKA

24
Q

Gq

A

activ PLC and PKC

incr Ca2+ via IP3R activ and SR Ca2+ release)

25
Q

Structure of PKA

A 
2 regulatory (each binds 2 cAMP)
2 catalytic units
26
Q

binding of ___ causes dissociation of dissociation of regulatory and catalytic subunit of PKA

A

4 cAMP - 2 to each cAMP

27
Q

HCN channels function

A

inward depolarizing current = funny current

28
Q

Activity of HCN incr by ___

A

sympathetic stim via cAMP binding

29
Q

HCN highly expressed where

A

SA myocytes for spontaneous AP

30
Q

Primary mechanism for parasympathetic control of HR

A

Activation of IK ach current

  • stabilize Vm near K+ equilibrium
  • incr outward K+ current, decr excitability
31
Q

Secondary mechanism of parasympathetic control of HR

A

inhibit inward current

hyperpol cell
decr excitability

32
Q

Difference between Vascular smooth muscle cells and cardiac myocytes

A

smooth = phosphorylation causes relaxation by inhib MLCK

skeletal = phosphorylation causes incr force of contraction

33
Q

What is the bainbridge reflex

A

low pressure baroreceptors in atria and vena cava incr HR in response to stretch

SPR2015 (23 decks)

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