Calcium Sensitization Mechanisms in Gastrointestinal Smooth Muscles

J Neurogastroenterol Motil. 2016 Apr 30;22(2):213-25. doi: 10.5056/jnm15186.


An increase in intracellular Ca(2+) is the primary trigger of contraction of gastrointestinal (GI) smooth muscles. However, increasing the Ca(2+) sensitivity of the myofilaments by elevating myosin light chain phosphorylation also plays an essential role. Inhibiting myosin light chain phosphatase activity with protein kinase C-potentiated phosphatase inhibitor protein-17 kDa (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation is considered to be the primary mechanism underlying myofilament Ca(2+) sensitization. The relative importance of Ca(2+) sensitization mechanisms to the diverse patterns of GI motility is likely related to the varied functional roles of GI smooth muscles. Increases in CPI-17 and MYPT1 phosphorylation in response to agonist stimulation regulate myosin light chain phosphatase activity in phasic, tonic, and sphincteric GI smooth muscles. Recent evidence suggests that MYPT1 phosphorylation may also contribute to force generation by reorganization of the actin cytoskeleton. The mechanisms responsible for maintaining constitutive CPI-17 and MYPT1 phosphorylation in GI smooth muscles are still largely unknown. The characteristics of the cell-types comprising the neuroeffector junction lead to fundamental differences between the effects of exogenous agonists and endogenous neurotransmitters on Ca(2+) sensitization mechanisms. The contribution of various cell-types within the tunica muscularis to the motor responses of GI organs to neurotransmission must be considered when determining the mechanisms by which Ca(2+) sensitization pathways are activated. The signaling pathways regulating Ca(2+) sensitization may provide novel therapeutic strategies for controlling GI motility. This article will provide an overview of the current understanding of the biochemical basis for the regulation of Ca(2+) sensitization, while also discussing the functional importance to different smooth muscles of the GI tract.

Keywords: Gastrointestinal motility; Myosin-light-chain phosphatase; Phosphorylation; Signal transduction; Smooth muscle.

Publication types

  • Review