Ion channel remodeling in gastrointestinal inflammation.
BACKGROUND
Gastrointestinal inflammation significantly affects the electrical excitability of smooth muscle cells. Considerable progress over the last few years have been made to establish the mechanisms by which ion channel function is altered in the setting of gastrointestinal inflammation. Details have begun to emerge on the molecular basis by which ion channel function may be regulated in smooth muscle following inflammation. These include changes in protein and gene expression of the smooth muscle isoform of L-type Ca(2+) channels and ATP-sensitive K(+) channels. Recent attention has also focused on post-translational modifications as a primary means of altering ion channel function in the absence of changes in protein/gene expression. Protein phosphorylation of serine/theronine or tyrosine residues, cysteine thiol modifications, and tyrosine nitration are potential mechanisms affected by oxidative/nitrosative stress that alter the gating kinetics of ion channels. Collectively, these findings suggest that inflammation results in electrical remodeling of smooth muscle cells in addition to structural remodeling.


OBJECTIVE
The purpose of this review is to synthesize our current understanding regarding molecular mechanisms that result in altered ion channel function during gastrointestinal inflammation and to address potential areas that can lead to targeted new therapies.
Akbarali
H I
HI
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, VCU Program in Enteric Neuromuscular Sciences (VPENS), Virginia Commonwealth University, Richmond, VA 23298, USA. hiakbarali@vcu.edu
G Hawkins
E
E
Ross
G R
GR
Kang
M
M
D000818:Animals; D015220:Calcium Channels / Q000096:biosynthesis / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003092:Colitis / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D050916:TRPV Cation Channels / Q000378:metabolism
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D007473:Ion Channels; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human