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Flashcards in regulation 2 Deck (32)
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Phospholamban (PLB) functions

1. relieves inhibition of SERCA
2. faster Ca2+ reuptake into SR.
3. Increases lusitropy.
4. Increases inotropy by increasing SR Ca2+ load.


Ryanodine Receptor (RyR) functions

1. Phosphorylation increases Ca2+ sensitivity,
2. Increases inotropy by increasing SR Ca2+ release.


L-type Ca2+ channel (DHPR)

1. Phosphorylation slows inactivation
2. increases entry of trigger Ca2+
3. Increased Ca2+-induced Ca2+ release increases inotropy


Troponin I (TnI)

1. P-TnI decreases Ca2+ sensitivity of troponin C
2. allows faster dissociation of Ca2+ so faster filling = increased lusitropy (not inotropy)


parasympathetic innervation of the ventricle is

sparse, so little parasympathetic regulation of inotropy


HR effect from symp and parasymp stim

Sympathetic stimulation increases heart rate

Parasympathetic stimulation decreases heart rate



Intrinsic Heart Rate and Basal Autonomic Tone


Propranolol blocks

β adrenergic receptors (sympathetic)


Atropine blocks

M2 muscarinic ACh receptors (parasympathetic)


Intrinsic heart rate is revealed by

block of both sympathetic and
parasympathetic tone.


Molecular Targets for sympathetic stimulation of chronotropy

1. Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs)
2. L-type Ca2+ channels and ryanodine receptors
3. Ryanodine receptors and Sodium-Calcium exchanger



Net inward (depolarizing) current = cardiac “funny current,” If


L-type Ca2+ channels

Net inward (depolarizing) current


RyRs function to

1. Increased trigger Ca2+ from L-type Ca2+ channel activates more Ca2+ release from SR via RyR
2. Ca2+ sensitivity of RyR increased by PKA phosphorylation


NCX function

Intracellular Ca2+ is extruded by NCX, which generates a net inward current (2 Ca2+ out, 3 Na+ in)


Inhibition of inward currents

1. hyperpolarizes cell
2. decreases excitability
3. secondary mechanisms for parasympathetic control of heart rate


Parasympathetic regulation of pacemaking is mediated by

release of acetylcholine (ACh) from vagal nerve endings in the sinoatrial node.


Parasympathetic regulation of pacemaking mechanism

1. ACh activates M2 muscarinic ACh receptors
2. which are coupled to the Gi/o heterotrimeric G protein.
3. Activation of Gi/o releases two signals:
a. the Gαi/o subunit and
b. the Gβγ subunit complex.


Molecular targets for parasympathetic inhibition of chronotropy

1. GIRKs
a. inhibit inward current
2. HCNs, L-type Ca2+ channels, and ryanodine receptors
a. activate I-k-ACh current


Activation of IKACh current

1. stabilizes Vm near K+ equilibrium potential
2. Increased outward K+ current decreases excitability
3. Primary mechanism for parasympathetic control of heart rate


Regulation of Arterial Pressure

1. Vascular Smooth Muscle
2. Neural control of the vasculature
3. Intrinsic control of the vasculature
4. Humoral control of the vasculature


Striated Muscle Contraction = ___ regulation

THIN filament regulation


Striated muscle at rest

1. troponin complex
2. Troponin I (inhibitory subunit) is bound to actin
3. Troponin T recruits tropomyosin
4. Tropomyosin blocks myosin binding site on actin


Troponin complex =

Troponin I, Troponin C, Troponin T


Striated muscle contraction

1. An action potential (required) triggers Ca2+ release from SR (CICR, EC coupling)
2. Ca2+ binds to troponin C, causes rearrangement of thin filament proteins
3. Myosin binding site on actin uncovered – permits cross bridge cycling
4. Contraction halted by removal of Ca2+


Vascular Smooth Muscle Cells (VSMCs)

1. Small mononucleate cells
2. No sarcomeres = smooth, not striated
3. No troponin complex, no tropomyosin
4. Different contractile mechanism vs. striated muscle (Ca2+ release from SR not required)
5. Rate of contraction slower than striated muscle, but can be sustained


Smooth Muscle Contraction = ___ regulation

thick filament


Smooth muscle contraction

1. triggered by mechanical, chemical, or electrical stimuli (APs not required)
2. Ca2+ enters cytoplasm from SR and/or plasma membrane Ca2+ channels
3. Ca2+ binds to Calmodulin (CaM)
4. Ca2+- CaM binds to Myosin Light Chain Kinase (MLCK), to activate it.
5. Activated MLCK phosphorylates the myosin head – permits cross bridge cycling
6. MLC dephosphorylated by Myosin Light Chain Phosphatase (MLCP), to halt contraction
7. cAMP (via PKA) inhibits MLCK – causes VSMC relaxation


Neural control of the vasculature includes:

1. Sympathetic regulation
2. Baroreceptor reflex
3. CNS control center


Sympathetic stimulation is usually