Cardiac Signaling Pathways/Vascular Signaling Pathways

Question 1

In a GPCR, what is bound during rest (GTP or GDP)

Answer 1

GDP

Question 2

How does sympathetic stimulation effect EC coupling?

Answer 2

PKA phosphorylates:
1. DHPR (L-type Ca Channel) slows inactivation

2. RyR- increasing Ca sensitivity
3. Troponin I (dec Ca sensitivity)
4. Phospholamban (inc SERCA activity which is Ca uptake into the sarcoplasmic reticulum)

Question 3

Which PLA-mediated phosphorylations increase Inotropy?

Answer 3

1. DHPR (L-type Ca Channel) slows inactivation
2. RyR- increasing Ca sensitivity
3. Phospholamban (PLB) increases inotropy by increasing SR Ca load.

Question 4

Which PLA-mediated phosphorylations increase lusitropy?

Answer 4

1. Troponin I- Decreases Ca sensitivity, allowing quicker inactivation of contraction.
2. Phospholamban (PLB) increases rate of removal of Ca from cytosol.**

Note PLB does inotropy and lusitropy

Question 5

How does the HCN channel increase heart rate?

Answer 5

GPCR–> cAMP binds to HCN channel–> Inc funny current (If)

Question 6

How does the L-type Ca channels increase heart rate?

Answer 6

GPCR–>cAMP–>PKA phosphoryalates L-type Ca channel–> Inc Ca influx–> depolarizes membrane

Question 7

How does the L-type Ca channels, RyRs and NCX (Na Ca exchanger) increase heart rate under sympathetic stimulation?

Answer 7

L-type–> Inc Ca–>activates RyR–> Inc Ca release from SR–> 1:3 Ca (out) to Na (in) exchange on membrane. This leads to an addition + charge and faster depolarization in the cell.

Look at her slide titled “sympathetic regulation of chronotropy: L-type Ca2+ channels, RYRs, and NCX

Question 8

How does the L-type Ca channels, RyRs and NCX (Na Ca exchanger) decrease heart rate under parasympathetic stimulation?

Answer 8

GPCR inhibitory alpha subunit Inhibits cAMP and PKA.

All effects are opposite of stimulation.

*this is secondary mechanism for parasympathetic control.

Question 9

What is the primary mechanism for parasympathetic control of chonotropy?

Answer 9

Ach binds GPCR-> Beta Gamma subunit go and activate GIRK channel.

GIRK is a K channel.

Question 10

Describe the differences between vascular smooth muscle cells and cardiac myocytes.

Answer 10

VSMC =

• Think Filament Regulation
• No Sarcomere
• Calmodulin (no troponin or tropomysin) activates MLCK

Question 11

True or False:

cAMP activates contraction in both smooth muscle and cardiac muscle

Answer 11

FALSE:

cAMP inhibits contraction in smooth muscle.

Question 12

What is the process for smooth muscle contraction?

Answer 12

1. Ca enters Cytoplasm from SR or ECM.
2. CA binds Calmodulin (CaM)
3. Ca-CaM activates Myosin light chain kinase (MLCK)
4. MLCK phosphorylates MLC and allows cross bridge cycling.

Question 13

How does the sympathetic response effect vasculature?

Answer 13

Norepinephrine binds to alpha (A1 and A2) adrenergic receptors causing VASOCONSTRICTION (usually).

Proceeds via the Gq second messanger system (IP3–> Ca release)

Question 14

How do baroreceptors effect vascular tone?

Answer 14

Inc in BP–> inc baroreceptor firing rate–> dec symp and inc para–>Vasodilation

Question 15

How do tissues change flow in capillaries to meet metabolic demand?

important

Answer 15

Via tissue metabolites.

Question 16

Name four tissue metabolites that control local flow to a capillary bed.

Answer 16

Inc CO2
Dec O2
Inc extracellular K+
Inc Adenosine (ATP metabolite)

Question 17

How does adenosine affect capillary tone?

Answer 17

It binds to A2 receptors and induces dilation.

Question 18

According to the myogenic response mechanism, lower extremity capillaries in a person who suddenly stands up would _____________ (dilate or constrict). Why?

Answer 18

Constrict.

Stretch activated Trp channels cause Ca influx to VSMCs (vascular smooth muscle cells).

Question 19

What effect does NO have on vasculature?

Answer 19

POTENT VASODILATOR.

Question 20

Where is NO produced?

Answer 20

In endothelial cells via cGMP pathway (similar to cAMP).

Question 21

What effect does endothelin have on vasculature?

Answer 21

VASOCONSTRICTION

Question 22

What is the primary system for long term control of blood pressure?

Answer 22

Renin-angiotensin-aldosterone System (RAAS)

Question 23

What does Angiontensinogen II do?

Answer 23

1. Causes Systemic Vasoconstriction

2. Stimulate Aldosterone and ADH production

Question 24

What do ADH and Aldosterone do to BP and Blood volume?

Answer 24

Increase both

Question 25

Where is atrial natriuretic peptide produced? What effect does it have on BP?

Answer 25

Produced by stretch receptors in the Right atrium.

Causes Vasodilation and natriuretic (sodium excretion)

Inhibits Aldosterone and ADG

Question 26

Describe the CV response to exercise in terms of Central command and local responses.

Answer 26

Central command: Inc Sympathetic tone–> Inc HR, Inotropy, Cardiac Output, Systemic Vasoconstricition, and Venous Return.

Local Response:
Inc Vasoactive metabolites–> Vasodilation in exercising muscle