regulation 2

Question 1

Phospholamban (PLB) functions

Answer 1

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

Question 2

Ryanodine Receptor (RyR) functions

Answer 2

1. Phosphorylation increases Ca2+ sensitivity,

2. Increases inotropy by increasing SR Ca2+ release.

Question 3

L-type Ca2+ channel (DHPR)

Answer 3

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

Question 4

Troponin I (TnI)

Answer 4

1. P-TnI decreases Ca2+ sensitivity of troponin C

2. allows faster dissociation of Ca2+ so faster filling = increased lusitropy (not inotropy)

Question 5

parasympathetic innervation of the ventricle is

Answer 5

sparse, so little parasympathetic regulation of inotropy

Question 6

HR effect from symp and parasymp stim

Answer 6

Sympathetic stimulation increases heart rate

Parasympathetic stimulation decreases heart rate

Question 7

Chronotropy:

Answer 7

Intrinsic Heart Rate and Basal Autonomic Tone

Question 8

Propranolol blocks

Answer 8

β adrenergic receptors (sympathetic)

Question 9

Atropine blocks

Answer 9

M2 muscarinic ACh receptors (parasympathetic)

Question 10

Intrinsic heart rate is revealed by

Answer 10

block of both sympathetic and

parasympathetic tone.

Question 11

Molecular Targets for sympathetic stimulation of chronotropy

Answer 11

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

Question 12

HCNs

Answer 12

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

Question 13

L-type Ca2+ channels

Answer 13

Net inward (depolarizing) current

Question 14

RyRs function to

Answer 14

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

Question 15

NCX function

Answer 15

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

Question 16

Inhibition of inward currents

Answer 16

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

Question 17

Parasympathetic regulation of pacemaking is mediated by

Answer 17

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

Question 18

Parasympathetic regulation of pacemaking mechanism

Answer 18

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.

Question 19

Molecular targets for parasympathetic inhibition of chronotropy

Answer 19

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

Question 20

Activation of IKACh current

Answer 20

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

Question 21

Regulation of Arterial Pressure

Answer 21

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

Question 22

Striated Muscle Contraction = ___ regulation

Answer 22

THIN filament regulation

Question 23

Striated muscle at rest

Answer 23

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

Question 24

Troponin complex =

Answer 24

Troponin I, Troponin C, Troponin T

Question 25

Striated muscle contraction

Answer 25

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+

Question 26

Vascular Smooth Muscle Cells (VSMCs)

Answer 26

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

Question 27

Smooth Muscle Contraction = ___ regulation

Answer 27

thick filament

Question 28

Smooth muscle contraction

Answer 28

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

Question 29

Neural control of the vasculature includes:

Answer 29

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

Question 30

Sympathetic stimulation is usually

Answer 30

vascocontriction

Question 31

L-type Ca2+ channels activity increased by

Answer 31

sympathetic stimulation

Question 32

L-type Ca2+ channels promote

Answer 32

excitability and spontaneous action potentials