Acid-sensing properties in rat gastric sensory neurons from normal and ulcerated stomach.
Gastric acid contributes to dyspeptic symptoms, including abdominal pain, in patients with disorders of the proximal gastrointestinal tract. To examine the molecular sensor(s) of gastric acid chemonociception, we characterized acid-elicited currents in dorsal root ganglion (DRG) and nodose ganglion (NG) neurons that innervate the stomach and examined their modulation after induction of gastric ulcers. A fluorescent dye (DiI) was injected into the stomach wall to retrogradely label gastric sensory neurons. After 1-2 weeks, gastric ulcers were induced by 45 s of luminal exposure of the stomach to 60% acetic acid injected into a clamped area of the distal stomach; control animals received saline. In whole-cell voltage-clamp recordings, all gastric DRG neurons and 55% of NG neurons exhibited transient, amiloride-sensitive, acid-sensing ion-channel (ASIC) currents. In the remaining 45% of NG neurons, protons activated a slow, sustained current that was attenuated by the transient receptor potential vanilloid subtype 1 antagonist, capsazepine. The kinetics and proton sensitivity of amiloride-sensitive ASIC currents differed between NG and DRG neurons. NG neurons had a lower proton sensitivity and faster kinetics, suggesting expression of specific subtypes of ASICs in the vagal and splanchnic innervation of the stomach. Effects of Zn2+ and N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine on acid-elicited currents suggest contributions of ASIC1a and ASIC2a subunits. Gastric ulcers altered the properties of acid-elicited currents by increasing pH sensitivity and current density and changing current kinetics in gastric DRG neurons. The distinct properties of NG and DRG neurons and their modulation after injury suggest differential contributions of vagal and spinal afferent neurons to chemosensation and chemonociception.
Sugiura
Takeshi
T
Department of Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA.
Dang
Khoa
K
Lamb
Kenneth
K
Bielefeldt
Klaus
K
Gebhart
G F
GF
D062565:Acid Sensing Ion Channels; D000143:Acids / Q000494:pharmacology; D000818:Animals; D005744:Gastric Acid / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000502:physiology*; D013270:Stomach / Q000187:drug effects / Q000502:physiology*; D013276:Stomach Ulcer / Q000503:physiopathology*
D062565:Acid Sensing Ion Channels; D000143:Acids; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels