Gastric ulcers reduce A-type potassium currents in rat gastric sensory ganglion neurons

被引:80
作者
Dang, K [1 ]
Bielefeldt, K
Gebhart, GF
机构
[1] Univ Iowa, Dept Pharmacol, Iowa City, IA 52242 USA
[2] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2004年 / 286卷 / 04期
关键词
stomach; visceral inflammation; hyperalgesia; dorsal root ganglia; nodose ganglia; voltage clamp; 4-aminopyridine; dendrotoxin; K+ currents;
D O I
10.1152/ajpgi.00258.2003
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:G573 / G579
页数:7
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