regulation

Question 1

Regulation of the CV system involves

Answer 1

coordinated control of the heart and vasculature

Question 2

GPCRs are

Answer 2

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

Question 3

A few cardiovascular GPCRs include:

Answer 3

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

Question 4

GPCR activation:

Answer 4

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.

Question 5

GPCR deactivation:

Answer 5

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

Question 6

Families of G proteins involved in cardiovascular function:

Answer 6

Gs, Gi/o, Gq.

Question 7

Gs and Gi/o are

Answer 7

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

Question 8

Gq activation

Answer 8

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

Question 9

b blockers are used to treat

Answer 9

arrhythmias, hypertension, and for cardioprotection post-MI

Question 10

angiotensin II receptor blockers

used to treat

Answer 10

hypertension and heart failure

Question 11

PKA is

Answer 11

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

Question 12

α1 adrenergic: G proteins

Answer 12

Gq

Question 13

β adrenergic: G protein

Answer 13

Gs

β1 and β2

Question 14

muscarinic Ach: G protein

Answer 14

Gi/o

Question 15

α1 adrenergic: signaling pathway

Answer 15

PLC, PKC → increases intracellular Ca2+

Question 16

β adrenergic: signaling pathway

Answer 16

1. stimulates adenylate cyclase

2. increases cAMP

Question 17

muscarinic Ach: signaling pathway

Answer 17

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

Question 18

α1 adrenergic: effects

Answer 18

vasoconstriction

Question 19

β adrenergic: effects

Answer 19

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

Question 20

muscarinic Ach: effects

Answer 20

decrease chronotropy

Question 21

autonomic regulation of inotrophy can be

Answer 21

1. sympathetic regulation of inotrophy

2. parasympathetic regulaiton of inotropy

Question 22

sympathetic regulation of inotrophy can be through

Answer 22

1. cAMP signaling

2. molecular targets for sympathetic regulation of inotropy and lusitropy

Question 23

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

Answer 23

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

Question 24

cAMP signaling

Answer 24

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

Question 25

PKA is

Answer 25

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.

Question 26

Gs functions

Answer 26

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

Question 27

Gi/o functions

Answer 27

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

Question 28

Gq functions

Answer 28

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

Question 29

Sympathetic stimulation increases inotropy via

Answer 29

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