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Flashcards in regulation Deck (29):
1

Regulation of the CV system involves

coordinated control of the heart and vasculature

2

GPCRs are

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

3

A few cardiovascular GPCRs include:

1. α & β adrenergic receptors,
2. acetylcholine receptors,
3. endothelin receptors,
4. adenosine receptors,
5. angiotensin II receptors.

4

GPCR activation:

1. agonist binds receptor,
2. GTP replaces GDP on α subunit of heterotrimeric
3. G protein causing dissociation of α and βγ G protein subunits.
4. Both α and βγ can be active signals.

5

GPCR deactivation:

auto dephosphorylation of GTP to GDP by α subunit permits reassociation with βγ. Rebinding of G protein to receptor causes inactivation.

6

Families of G proteins involved in cardiovascular function:

Gs, Gi/o, Gq.

7

Gs and Gi/o are

stimulatory & inhibitory, respectively, for cAMP production by adenylate
cyclase.

8

Gq activation

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

9

b blockers are used to treat

arrhythmias, hypertension, and for cardioprotection post-MI

10

angiotensin II receptor blockers
used to treat

hypertension and heart failure

11

PKA is

1. cAMP dependent protein kinase
2. has 2 regulatory and 2 catalytic subunits
3. binding of 4 cAMP molecules causes dissociation
4. free catalytic subunit can phosphorylate target proteins

12

α1 adrenergic: G proteins

Gq

13

β adrenergic: G protein

Gs
(β1 and β2)

14

muscarinic Ach: G protein

Gi/o

15

α1 adrenergic: signaling pathway

PLC, PKC → increases intracellular Ca2+

16

β adrenergic: signaling pathway

1. stimulates adenylate cyclase
2. increases cAMP

17

muscarinic Ach: signaling pathway

1. inhibits adenylate cyclase
2. decreases cAMP
3. releases βγ subunits

18

α1 adrenergic: effects

vasoconstriction

19

β adrenergic: effects

1. heart: increase chronotropy, inotropy, lusitropy, dromotropy

2. vascular beds in skeletal muscle: vasodilation

20

muscarinic Ach: effects

decrease chronotropy

21

autonomic regulation of inotrophy can be

1. sympathetic regulation of inotrophy
2. parasympathetic regulaiton of inotropy

22

sympathetic regulation of inotrophy can be through

1. cAMP signaling
2. molecular targets for sympathetic regulation of inotropy and lusitropy

23

molecular targets for sympathetic regulation of inotropy and lusitropy can be through

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

24

cAMP signaling

1. Sympathetic neurons innervate the heart, release NE,
2. NE binds to β adrenergic receptors to increase cAMP.
2. Phosphodiesterases breaks down cAMP (and cGMP) and help to establish intracellular signaling microdomains and specificity of signaling
3. PKA

25

PKA is

1. cAMP-dependent protein kinase.
2. Major effector for cAMP signaling in heart.
3. Phosphorylates target proteins (counterpart = phosphatases that dephosphorylate targets).
4. Phosphorylation changes protein function by changing conformation and charge.

26

Gs functions

1. stimulatory G protein
2. activates adenylate cyclase
3. increases cAMP
4. activated PKA

27

Gi/o functions

1. inhibitory G protein
2. inhibits adenylate cyclase
3. decreases cAMP
4. inhibits PKA

28

Gq functions

1. quirky G protein
2. activated PLC
3. activated PKC
4. increases Ca2+
(via IP3R activation and SR Ca2+ release)

29

Sympathetic stimulation increases inotropy via

PKA phosphorylation of at least 4 proteins involved in EC coupling.