Cardiac Signaling Pathways/Vascular Signaling Pathways Flashcards
In a GPCR, what is bound during rest (GTP or GDP)
GDP
How does sympathetic stimulation effect EC coupling?
PKA phosphorylates:
1. DHPR (L-type Ca Channel) slows inactivation
- RyR- increasing Ca sensitivity
- Troponin I (dec Ca sensitivity)
- Phospholamban (inc SERCA activity which is Ca uptake into the sarcoplasmic reticulum)
Which PLA-mediated phosphorylations increase Inotropy?
- DHPR (L-type Ca Channel) slows inactivation
- RyR- increasing Ca sensitivity
- Phospholamban (PLB) increases inotropy by increasing SR Ca load.
Which PLA-mediated phosphorylations increase lusitropy?
- Troponin I- Decreases Ca sensitivity, allowing quicker inactivation of contraction.
- Phospholamban (PLB) increases rate of removal of Ca from cytosol.**
Note PLB does inotropy and lusitropy
How does the HCN channel increase heart rate?
GPCR–> cAMP binds to HCN channel–> Inc funny current (If)
How does the L-type Ca channels increase heart rate?
GPCR–>cAMP–>PKA phosphoryalates L-type Ca channel–> Inc Ca influx–> depolarizes membrane
How does the L-type Ca channels, RyRs and NCX (Na Ca exchanger) increase heart rate under sympathetic stimulation?
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
How does the L-type Ca channels, RyRs and NCX (Na Ca exchanger) decrease heart rate under parasympathetic stimulation?
GPCR inhibitory alpha subunit Inhibits cAMP and PKA.
All effects are opposite of stimulation.
*this is secondary mechanism for parasympathetic control.
What is the primary mechanism for parasympathetic control of chonotropy?
Ach binds GPCR-> Beta Gamma subunit go and activate GIRK channel.
GIRK is a K channel.
Describe the differences between vascular smooth muscle cells and cardiac myocytes.
VSMC =
- Think Filament Regulation
- No Sarcomere
- Calmodulin (no troponin or tropomysin) activates MLCK
True or False:
cAMP activates contraction in both smooth muscle and cardiac muscle
FALSE:
cAMP inhibits contraction in smooth muscle.
What is the process for smooth muscle contraction?
- Ca enters Cytoplasm from SR or ECM.
- CA binds Calmodulin (CaM)
- Ca-CaM activates Myosin light chain kinase (MLCK)
- MLCK phosphorylates MLC and allows cross bridge cycling.
How does the sympathetic response effect vasculature?
Norepinephrine binds to alpha (A1 and A2) adrenergic receptors causing VASOCONSTRICTION (usually).
Proceeds via the Gq second messanger system (IP3–> Ca release)
How do baroreceptors effect vascular tone?
Inc in BP–> inc baroreceptor firing rate–> dec symp and inc para–>Vasodilation
How do tissues change flow in capillaries to meet metabolic demand?
important
Via tissue metabolites.
Name four tissue metabolites that control local flow to a capillary bed.
Inc CO2
Dec O2
Inc extracellular K+
Inc Adenosine (ATP metabolite)
How does adenosine affect capillary tone?
It binds to A2 receptors and induces dilation.
According to the myogenic response mechanism, lower extremity capillaries in a person who suddenly stands up would _____________ (dilate or constrict). Why?
Constrict.
Stretch activated Trp channels cause Ca influx to VSMCs (vascular smooth muscle cells).
What effect does NO have on vasculature?
POTENT VASODILATOR.
Where is NO produced?
In endothelial cells via cGMP pathway (similar to cAMP).
What effect does endothelin have on vasculature?
VASOCONSTRICTION
What is the primary system for long term control of blood pressure?
Renin-angiotensin-aldosterone System (RAAS)
What does Angiontensinogen II do?
- Causes Systemic Vasoconstriction
2. Stimulate Aldosterone and ADH production
What do ADH and Aldosterone do to BP and Blood volume?
Increase both
