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Intensive Care Medicine Experimental
Figure 1 | Intensive Care Medicine Experimental

Figure 1

From: Calcium desensitisation in late polymicrobial sepsis is associated with loss of vasopressor sensitivity in a murine model

Figure 1

Smooth muscle cell contraction depends on Ca 2+ -dependent and Ca 2+ -independent pathways. Actin-myosin cross bridge cycling and smooth muscle contraction depend on phosphorylation of the myosin light chain by Ca2+: calmodulin (CaM)-dependent myosin light-chain kinase (MLCK). Relaxation is favoured by myosin light-chain phosphatase (MLCP) as the active subunit removes the phosphoryl group from the myosin light chain. Cytosolic [Ca2+] is derived from (i) the extracellular space (through voltage-operated Ca2+ channels (VOCC; predominantly Cav1.2 L-type Ca2+ channels) and receptor-operated non-specific cation channels (ROCC)) or (ii) IP3-dependent release from the sarcoplasmic reticulum (SR). MLCP is inhibited, favouring contraction, either through (i) direct inhibition by PKC-dependent CPI-17 or (ii) inhibitory phosphorylation of the regulatory subunit MYPT by RhoA-dependent Rho kinase. α1-adrenergic G protein-coupled receptors (GPCR) activate all four contractile pathways: VOCC/ROCC, IP3/SR, PKC/CPI-17 and RhoA/ROK; TxA2 GPCR activate VOCC and RhoA/ROK; PDBu activates PKC/CPI-17 whilst high-[K+]-mediated depolarisation activates VOCC. PLC, phospholipase C; PIP2, phosphatidylinositol 4,5-bisphosphate; DAG, diacylglycerol; IP3, inositol triphosphate.

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