FIGURE 7. Calcium-dependent and -independent contractions in vascular smooth muscle cells.


Calcium-dependent and -independent contractions in vascular smooth muscle cells. The stimulation of G-protein-coupled cell membrane receptors evokes a contractile response that, depending on the G-protein involved, implies different coupling mechanisms. Gq-coupled receptors (e.g., α1-adrenergic receptor) produce calcium-dependent and -independent contractions. The activation of phospholipase C (PLC) and the subsequent production of inositol trisphosphate (IP3) release calcium from intracellular stores (sarcoplasmic reticulum, SR). Stimulation of TRP channels, possibly by diacylglycerol (DAG), such as TRPC3 and TRPC6, allows calcium entry and produces depolarization, which in turn activates voltage-gated calcium channels (CaV). The increase in the concentration of intracellular calcium ([Ca2+]i) activates calmodulin (CaM) which allow the phosphorylation of myosin (myosin-P) by the myosin light chain kinase (MLCK) and the establishment of the bond with actin. The production of DAG activates the calcium-independent protein kinase C (PKC) pathway. PKC activates the PKC-potentiated inhibitory protein of 17 kDa (CPI-17) which inhibits the myosin light chain phosphatase (MLCP), preventing the dephosphorylation of myosin. Additionally, PKC may activate RhoA and Rho kinase which, in a calcium-independent manner, activates myosin light chain kinase and inhibits myosin light chain phosphatase. The stimulation of the G12/13-coupled receptors (e.g., receptor for thromboxane A2, TP receptor) produces a virtually calcium-independent contraction via the activation of Rho guanine nucleotide exchange factor (Rho-GEF) and the Rho-kinase pathway. The various proteins involved in the contraction of the vascular smooth muscle cells are heavily regulated for instance by the cyclic-AMP-dependent protein kinase A (PKA) or the cyclic-GMP (cGMP)-dependent protein kinase G.

From: Chapter 3, Calcium Signaling in Vascular Cells and Cell-to-Cell Communications

Cover of The Endothelium
The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators.
Félétou M.
San Rafael (CA): Morgan & Claypool Life Sciences; 2011.
Copyright © 2011 by Morgan & Claypool Life Sciences Publishers.

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