High resolution

Module 7: Figure smooth muscle cell E-C coupling

Smooth muscle cell excitation–contraction (E-C) coupling mechanisms.

A network of signalling pathways is responsible for smooth muscle excitation–contraction (E-C) coupling. Ca2+ is derived from three sources: it can enter the cell through L-type voltage-operated channels (VOCs), it can be released by ryanodine receptors (RYRs) from internal stores or it can be released by inositol 1,4,5-trisphosphate (IP3). Ca2+ acts through calmodulin (CaM) to stimulate a myosin light chain kinase (MLCK), which phosphorylates the regulatory myosin light chain (MLC) to enable the myosin heads to interact with actin to initiate the contraction cycles. Sensitization of the Ca2+ signalling system is carried out through a Rho/Rho kinase signalling pathway that phosphorylates a myosin phosphatase targeting subunit 1 (MYPT1), which then inactivates the catalytic protein phosphatase 1 (PP1) to prevent it from dephosphorylating the regulatory light chains.