Via vagus nerve
* Originate in medulla oblongata
[WG21:p608(fig31-8)]
[BL8:p88(fig4-4)]
Stimulates muscarinic acetylcholine receptors (M2)
--> Coupled with Gi protein
--> Inhibits adenylyl cyclase
--> Decrease cAMP
--> Decrease conductance of Ca2+
--> Decrease myocardial contractility
Also,
--> Gi protein is coupled to a K+ channel
--> Increased K+ conductance
--> Decreased RMP
--> Decrease HR (when acting on nodes)
Also,
Originate in intermediolateral column of upper 5-6 thoracic and lower 1 or 2 cervical segements of the spinal cord
Stimulates beta-1 receptor
--> via Gs protein
--> Activate adenylyl cyclase
--> Increase cAMP
--> Activate protein kinase A
--> Phosphorylation of Ca2+ channels on membrane
--> Channels open for longer
--> Greater Ca2+ influx
--> Greater contractility
Also,
Protein kinase A
--> Phosphorylation of phospholamban
--> Stimulation of calcium pump on SR
--> Increased active transport of Ca2+ to SR
--> Faster relaxation
[BL8:p105]
Plus,
Protein kinase A
--> Phosphorylation of Troponin I
--> Inhibition of Ca2+ binding by Troponin C
--> Relaxation
--> Faster relaxation
NB:
At rest, there is a certain level of vagal tone at rest.
When vagus is cut, HR increase from 70 to 150-180 because sympathetic tone is unopposed.
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