Gastric ulcers reduce A-type potassium currents in rat gastric sensory ganglion neurons.
Voltage-dependent potassium currents are important contributors to neuron excitability and thus also to hypersensitivity after tissue insult. We hypothesized that gastric ulcers would alter K(+) current properties in primary sensory neurons. The rat stomach was surgically exposed, and a retrograde tracer (1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanine methanesulfonate) was injected into multiple sites in the stomach wall. Inflammation and ulcers were produced by 10 injections of 20% acetic acid (HAc) in the gastric wall. Saline (Sal) injections served as control. Nodose or T9-10 dorsal root ganglia (DRG) cells were harvested and cultured 7 days later to record whole cell K(+) currents. Gastric sensory neurons expressed transient and sustained outward currents. Gastric inflammation significantly decreased the A-type K(+) current density in DRG and nodose neurons (Sal vs. HAc-DRG: 82.9 +/- 7.9 vs. 46.5 +/- 6.1 pA/pF; nodose: 149.2 +/- 10.9 vs. 71.4 +/- 11.8 pA/pF), whereas the sustained current was not altered. In addition, there was a significant shift in the steady-state inactivation to more hyperpolarized potentials in nodose neurons (Sal vs. HAc: -76.3 +/- 1.0 vs. -83.6 +/- 2.2 mV) associated with an acceleration of inactivation kinetics. These data suggest that a reduction in K(+) currents contributes, in part, to increased neuron excitability that may lead to development of dyspeptic symptoms.
Dang
K
K
Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA. khoa-dang@uiowa.edu
Bielefeldt
K
K
Gebhart
G F
GF
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004546:Elapid Venoms / Q000494:pharmacology; D004594:Electrophysiology; D017950:Ganglia, Sensory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000378:metabolism*; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D004546:Elapid Venoms; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C020273:dendrotoxin; D015761:4-Aminopyridine