Calcium Sensitization Mechanisms in Gastrointestinal Smooth Muscles.
Authors Perrino BA
Submitted By Brian Perrino on 10/25/2016
Status Published
Journal Journal of neurogastroenterology and motility
Year 2016
Date Published
Volume : Pages 22 : 213 - 25
PubMed Reference 26701920
Abstract 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.

Investigators with authorship
Brian PerrinoUniversity of Nevada-Reno