Ca²⁺ sensitisation and desensitisation mechanisms in pulmonary artery

Modulation of Ca²⁺sensitivity of the smooth muscle contractile apparatus plays a fundamental role in the regulation of force. Increased CA²⁺ sensitivity may contribute towards various disease conditions such as pulmonary hypertension. Ca²⁺ sensitivity is regulated by the balance between myosin light chain kinase (MLCK)-dependent phosphorylation and myosin phosphatase (MP)-dependent dephosphorylation of myosin light chain (MLC-20). Several protein kinases have been implicated in modulating this process. In particular RhoA and its effector Rho kinase (Rhok) inhibits MP activity via the MYPTl subunit; whereas protein kinase C (PKC) activates MP inhibitory protein CPI-17. Additionally the mitogen activated protein kinases (MAPK) and heat shock protein 27 (HSP27) may effectively modulate Ca²⁺ sensitivity via the cytoskeleton.EThOS - Electronic Theses Online ServiceGBUnited Kingdo