TY - JOUR
T1 - Biophysically based modeling of the interstitial cells of Cajal
T2 - Current status and future perspectives
AU - Lees-Green, Rachel
AU - Du, Peng
AU - O'Grady, Gregory
AU - Beyder, Arthur
AU - Farrugia, Gianrico
AU - Pullan, Andrew J.
PY - 2011
Y1 - 2011
N2 - Gastrointestinal motility research is progressing rapidly, leading to significant advances in the last 15years in understanding the cellular mechanisms underlying motility, following the discovery of the central role played by the interstitial cells of Cajal (ICC). As experimental knowledge of ICC physiology has expanded, biophysically based modeling has become a valuable tool for integrating experimental data, for testing hypotheses on ICC pacemaker mechanisms, and for applications in in silico studies including in multiscale models. This review is focused on the cellular electrophysiology of ICC. Recent evidence from both experimental and modeling domains have called aspects of the existing pacemaker theories into question. Therefore, current experimental knowledge of ICC pacemaker mechanisms is examined in depth, and current theories of ICC pacemaking are evaluated and further developed. Existing biophysically based ICC models and their physiological foundations are then critiqued in light of the recent advances in experimental knowledge, and opportunities to improve these models are identified. The review concludes by examining several potential clinical applications of biophysically based ICC modeling from the subcellular through to the organ level, including ion channelopathies and ICC network degradation.
AB - Gastrointestinal motility research is progressing rapidly, leading to significant advances in the last 15years in understanding the cellular mechanisms underlying motility, following the discovery of the central role played by the interstitial cells of Cajal (ICC). As experimental knowledge of ICC physiology has expanded, biophysically based modeling has become a valuable tool for integrating experimental data, for testing hypotheses on ICC pacemaker mechanisms, and for applications in in silico studies including in multiscale models. This review is focused on the cellular electrophysiology of ICC. Recent evidence from both experimental and modeling domains have called aspects of the existing pacemaker theories into question. Therefore, current experimental knowledge of ICC pacemaker mechanisms is examined in depth, and current theories of ICC pacemaking are evaluated and further developed. Existing biophysically based ICC models and their physiological foundations are then critiqued in light of the recent advances in experimental knowledge, and opportunities to improve these models are identified. The review concludes by examining several potential clinical applications of biophysically based ICC modeling from the subcellular through to the organ level, including ion channelopathies and ICC network degradation.
KW - Electrophysiology
KW - Gastrointestinal motility
KW - Interstitial cells of Cajal
KW - Ion channels
KW - Mathematical models
KW - Pacemaker
KW - Physiome
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U2 - 10.3389/fphys.2011.00029
DO - 10.3389/fphys.2011.00029
M3 - Review article
C2 - 21772822
AN - SCOPUS:84864572552
SN - 1664-042X
VL - JUL
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - Article 29
ER -