Absence of PKD1 and mechanosensitivity

•Dissect 3rd order arteries•Incubate in papain/DTT @ 37 ° C•Incubate in Collagenase F/H @ 37 ° C•Triturate•Let rest 1 hour @ 4°C•Start recording•Use cells within 5 hours post 4 ° C

Smooth muscle -actinHoechst nuclear stain

Acute dissociation of mesenteric smooth muscle cells

1.5 pA

Cre

N = 20

1.5 pA

Cre Lox/Lox/Cre

N = 20 N = 48

Cell attached

Cell attached

• Myogenic response: ability of vascular smooth muscle to constrict in response to an increase in transmural pressure, or dilate in response to reduced transmural pressure.

• Myogenic response is essential for setting of vascular resistance.

• The mechanism of pressure sensing remains to be determined.

Techniques expérimentales

Artériographie isobarique

150 µm

Artères mésentériquesSouris transgéniques

Increase in intraluminal pressure

VSM membrane stretch

VSM membrane depolarization

Opening of voltage-gated Ca2+ channels

Ca2+ influx

Phosphorylation of MLCK

Activation of Ca2+/CaMK

Phosphorylation of MLC

Contraction

Steps in the myogenic response

Is myogenic tone altered in pkd1del mice?

Tonus myogénique

Increase in intraluminal pressure

VSM membrane stretch

VSM membrane depolarization

Opening of voltage-gated Ca2+ channels

Ca2+ influx

Phosphorylation of MLCK

Activation of Ca2+/CaMK

Phosphorylation of MLC

Contraction

Steps in the myogenic response

Is myogenic tone altered in pkd1del mice?

I. D.

O. D.

Conclusion

• Mechanosensitivity of smooth muscle cells of resistance arteries is sign. reduced in PKD1del mice.

• Myogenic tone is significantly reduced in PKD1del mice.

• The threshold for the myogenic tone is shifted to higher pressure values in PKD1del mice.

• Responses to PHE and K are unaltered in PKD1del mice.

• Passive properties are unaltered between the different genotypes.