Sinus node essay

Question 1

Molecular events in embryological development of SAN

Answer 1

• Pitx2 repression of PMP in the left atrial region
• Isl1 and Shox2 initiate PMP
• Repression of WCMP with Isl1 Shox2, Tbx18(in head), Nkx2.5 (tail) and Tbx3
• SAN cells develop different expression of channels and have different AP

Question 2

Anatomy of SAN

Answer 2

• Node is localised between IVC and SVC in the RA

- Has a head and tail

Question 3

Histology of SAN

Answer 3

• Contains specialised PM myocytes
• El spindle: Tranisition impulse to crista terminalis
• Spindle
• Spider: may be source of AP
• Non-myocytes: many fibroblasts and node rich in collagen

Question 4

Channel expression

Answer 4

• Head: Cav1.3, Cav3.1, HCN4, Hcn2, Hcn1,

- Tail: Less HCN, some Nav1.5

Question 5

PMC AP

Answer 5

• Sinusoidal AP as no resting potential or plateau

- HCN hyperpolarised-activation initiates the PM potential

Question 6

SAN response to stress

Answer 6

• Triggered by adrenergic stim (innervation- NOR and circulating Ad)
• B1-AR activate Gs (ligand binds, conformation change, beta-gamma and alpha-s dissociate
• Alpha-s activates adenylyl cyclase
• cAMP produced
• cAMP activates PKA and opens Ca channels
• PKA increases If, ICa,

Question 7

2nd HF in PM development

Answer 7

• Posterior and anterior compartments

Question 8

Initial PM potential

Answer 8

• Originates on the left in the linear heart tube
• Maintained on the left after cardiac looping
• Some become atrial myocardium due to Pitx2, Nkx2.5 and Tbx5

Question 9

Tbx TFs

Answer 9

Tbx5, Tbx20
- Specify chamber myocardium

Tbx18 (Ptx2 inh), Tbx3
- Specify PMC

Question 10

SAN vs WCM

Answer 10

GJ: 30.2 vs 40,43

Upstroke: slow vs fast (Nav1.5)

Question 11

3rd HF

Answer 11

• Unique cell group in a very posterior position on the right side
• Wnt8 (crescent inh)