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1

Molecular events in embryological development of SAN

- 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

2

Anatomy of SAN

- Node is localised between IVC and SVC in the RA

- Has a head and tail

3

Histology of SAN

- 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

4

Channel expression

- Head: Cav1.3, Cav3.1, HCN4, Hcn2, Hcn1,
- Tail: Less HCN, some Nav1.5

5

PMC AP

- Sinusoidal AP as no resting potential or plateau

- HCN hyperpolarised-activation initiates the PM potential

6

SAN response to stress

- 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,

7

2nd HF in PM development

- Posterior and anterior compartments

8

Initial PM potential

- 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


9

Tbx TFs

Tbx5, Tbx20
- Specify chamber myocardium

Tbx18 (Ptx2 inh), Tbx3
- Specify PMC

10

SAN vs WCM

GJ: 30.2 vs 40,43

Upstroke: slow vs fast (Nav1.5)

11

3rd HF

- Unique cell group in a very posterior position on the right side

- Wnt8 (crescent inh)