title: Dynamic excitation states and firing patterns are controlled by sodium channel kinetics in myenteric neurons: a simulation study.
abstract: Enteric neurons located in the gastro-intestinal tract are of particular importance to control digestive functions such as motility and secretion. In our recent publication, we showed that mouse myenteric neurons exhibit 2 types of tetrodotoxin-resistant Na(+) currents: a fast inactivating Na(+) current produced by Nav1.5 channels, present in nearly all myenteric neurons, and a persistent Na(+) current attributed to Nav1.9 channels, restricted to the intrinsic primary afferent neurons (IPANs). By combination of experimental recording and computer simulation we found that Nav1.5 contributed to the upstroke velocity of action potentials (APs), whereas Nav1.9 opposed AP repolarization. Here, we detailed the Na(+), Ca(2+) and K(+) currents used in our computational model of IPAN. We refined the prototype cell to reproduce the sustained firing pattern recorded in situ. As shown in experimental conditions we demonstrated that Nav1.9 channels critically determine the up-state life-time and thus, are essential to sustain tonic firing.
authors.affiliation: a International Center for Molecular Physiology (Dnipropetrovsk Division); National Academy of Sciences of Ukraine ; Kiev , Ukraine.
authors.forename: Sergiy M
authors.initials: SM
authors.lastname: Korogod
authors.forename: Nancy
authors.initials: N
authors.lastname: Osorio
authors.forename: Iryna B
authors.initials: IB
authors.lastname: Kulagina
authors.forename: Patrick
authors.initials: P
authors.lastname: Delmas
mesh_terms: D000200:Action Potentials; D000818:Animals; D007700:Kinetics; D051379:Mice; D008959:Models, Neurological; D009197:Myenteric Plexus / Q000166:cytology / Q000502:physiology*; D062558:NAV1.9 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology*
chemical_list: D062558:NAV1.9 Voltage-Gated Sodium Channel
keywords: AP, Action Potential; ENS, Enteric Nervous System; IPAN, Intrinsic Primary Afferent Neuron; Nav1.5; Nav1.9; WT, Wild Type; action potential; enteric neuron; gastro-intestinal disease; intestinal tract; neuronal firing; sodium channel