Regulation of the Cardiovascular System Flashcards
7-transmembrane-spanning integral membrane proteins
Extremely important for intracellular signaling throughout body
G protein-coupled receptors (GPCRs)
used to treat arrhythmias, hypertension, and for cardioprotection post-MI
many subtypes
b blockers
GPCRs are the most prevalent drug target!
used to treat hypertension and heart failure
angiotensin II receptor blockers
GPCRs are the most prevalent drug target!
stimulatory G protein
activates adenylate cyclase
ncreases cAMP, activates PIKA
Gs
inhibitory G protein
inhibits adenylate cyclase
Decreases cAMP, inhibits PKA
Gi/o
activates PLC and PKC
Increases Ca2+ (via IP3R activation & SR Ca2+ release)
Gq
Sympathetic stimulation increases inotropy
Little parasympathetic regulation of ______
inotropy
Sympathetic stimulation increases inotropy via ________ of 4 proteins involved in EC coupling.
PKA phosphorylation
relieves inhibition of SERCA
faster Ca2+ reuptake into SR.
Increases lusitropy.
Increases inotropy by increasing SR Ca2+ load.
PKA phosphorylation of Phospholamban (PLB)
_______ stimulation increases inotropy
Little parasympathetic regulation of inotropy
Sympathetic
Phosphorylation increases Ca2+ sensitivity,
Increases inotropy by increasing SR Ca2+ release.
PKA phosphorylation of Ryanodine Receptor (RyR)
Phosphorylation slows inactivation, increases entry of trigger Ca2+
Increased Ca2+-induced Ca2+ release increases inotropy
PKA phosphorylation of L-type Ca2+ channel (DHPR)
decreases Ca2+ sensitivity of troponin C
allows faster dissociation of Ca2+ so faster filling = increased lusitropy (not inotropy)
PKA phosphorylation of Troponin I (TnI)
chronotropy
Chronotropic effects are those that change the heart rate.
Propranolol blocks β adrenergic receptors ___________
(sympathetic)
Atropine blocks muscarinic ACh receptors _________
(parasympathetic)
Net inward (depolarizing) current = cardiac “funny current,” If
Promotes excitability and spontaneous action potentials
Highly expressed in sinoatrial myocytes
Activity increased by sympathetic stimulation via cAMP binding
HCNs
Contractile proteins in striated muscle are organized in sarcomeres
Actin thin filaments
Myosin thick filaments
Small mononucleate cells
No sarcomeres
No troponin complex, no tropomyosin
Ca2+ release from SR not required
Vascular Smooth Muscle Cells (VSMCs)
Contraction triggered by mechanical, chemical, or electrical stimuli (APs not required)
Smooth Muscle Contraction: THICK filament regulation
Ca2+- CaM binds to ________, to activate it. when activated, phosphorylates the myosin head permits cross bridge cycling in smooth muscle
Myosin Light Chain Kinase (MLCK)
MLC dephosphorylated by Myosin Light Chain Phosphatase (MLCP), to ______
halt contraction in smooth muscle
**cAMP (via PKA) inhibits MLCK – causes VSMC relaxation
cAMP (via PKA) inhibits MLCK – causes __________
VSMC relaxation
Sympathetic stimulation =
VASOCONSTRICTION (usually)