Flashcards in regulation Deck (29):
Regulation of the CV system involves
coordinated control of the heart and vasculature
7-transmembrane- spanning (7TM) integral membrane proteins that transduce ligand binding to intracellular signaling.
A few cardiovascular GPCRs include:
1. α & β adrenergic receptors,
2. acetylcholine receptors,
3. endothelin receptors,
4. adenosine receptors,
5. angiotensin II receptors.
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.
auto dephosphorylation of GTP to GDP by α subunit permits reassociation with βγ. Rebinding of G protein to receptor causes inactivation.
Families of G proteins involved in cardiovascular function:
Gs, Gi/o, Gq.
Gs and Gi/o are
stimulatory & inhibitory, respectively, for cAMP production by adenylate
increases intracellular Ca2+ via activation of phospholipase C (PLC) and
Protein Kinase C (PKC).
b blockers are used to treat
arrhythmias, hypertension, and for cardioprotection post-MI
angiotensin II receptor blockers
used to treat
hypertension and heart failure
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
α1 adrenergic: G proteins
β adrenergic: G protein
(β1 and β2)
muscarinic Ach: G protein
α1 adrenergic: signaling pathway
￼PLC, PKC → increases intracellular Ca2+
β adrenergic: signaling pathway
1. stimulates adenylate cyclase
2. increases cAMP
muscarinic Ach: signaling pathway
1. inhibits adenylate cyclase
2. decreases cAMP
3. releases βγ subunits
α1 adrenergic: effects
β adrenergic: effects
1. heart: increase chronotropy, inotropy, lusitropy, dromotropy
2. vascular beds in skeletal muscle: vasodilation
muscarinic Ach: effects
autonomic regulation of inotrophy can be
1. sympathetic regulation of inotrophy
2. parasympathetic regulaiton of inotropy
sympathetic regulation of inotrophy can be through
1. cAMP signaling
2. molecular targets for sympathetic regulation of inotropy and lusitropy
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)
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
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.
1. stimulatory G protein
2. activates adenylate cyclase
3. increases cAMP
4. activated PKA
1. inhibitory G protein
2. inhibits adenylate cyclase
3. decreases cAMP
4. inhibits PKA
1. quirky G protein
2. activated PLC
3. activated PKC
4. increases Ca2+
(via IP3R activation and SR Ca2+ release)