Electrophysiological identification of glucose-sensing neurons in rat nodose ganglia

Abstract

The vagal afferent system is strategically positioned to mediate rapid changes in motility and satiety in response to systemic glucose levels. In the present study we aimed to identify glucose-excited and glucose-inhibited neurons in nodose ganglia and characterize their glucose-sensing properties. Whole-cell patch-clamp recordings in vagal afferent neurons isolated from rat nodose ganglia demonstrated that 31/118 (26%) neurons were depolarized after increasing extracellular glucose from 5 to 15 mm; 19/118 (16%) were hyperpolarized, and 68/118 were non-responsive. A higher incidence of excitatory response to glucose occurred in gastric-than in portal vein-projecting neurons, the latter having a higher incidence of inhibitory response. In glucose-excited neurons, elevated glucose evoked membrane depolarization (11 mV) and an increase in membrane input resistance (361 to 437 M ). Current reversed at −99 mV. In glucose-inhibited neurons, membrane hyperpolarization (−13 mV) was associated with decreased membrane input resistance (383 to 293 M ). Current reversed at −97 mV. Superfusion of tolbutamide, a K ATP channel sulfonylurea receptor blocker, elicited identical glucose-excitatory but not glucose-inhibitory responses. Kir6.2 shRNA transfection abolished glucose-excited but not glucose-inhibited responses. Phosphatidylinositol bisphosphate (PIP 2 ) depletion using wortmannin increased the fraction of glucose-excited neurons from 26% to 80%. These results show that rat nodose ganglia have glucose-excited and glucose-inhibited neurons, differentially distributed among gastric-and portal vein-projecting nodose neurons. In glucose-excited neurons, glucose metabolism leads to K ATP channel closure, triggering membrane depolarization, whereas in glucose-inhibited neurons, the inhibitory effect of elevated glucose is mediated by an ATP-independent K + channel. The results also show that PIP 2 can determine the excitability of glucose-excited neurons.

Mercaptoacetate and fatty acids exert direct and antagonistic effects on nodose neurons via GPR40 fatty acid receptors

“…However, diazoxide had no effect on the FA-induced increase in cytosolic calcium in nodose neurons. This result is not due to the absence of this channel in nodose neurons, since effects of glucose on glucoseexcited nodose neurons have been shown to be mediated by the K ATP channel (15). Our finding that FA effects in nodose neurons are independent of this channel suggests that these effects do not require changes in ATP levels in these neurons.…”

Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents

“…Each esophagus received three injections. Four nodose ganglia (2 from each animal) were collected 10 days later and processed for whole cell patch-clamp recordings, as we previously described (12). Briefly, nodose ganglia from normal guinea pigs were minced in a 35-mm culture dish (containing Ca 2ϩ -and Mg 2ϩ -free Hanks' balanced salt solution with penicillin and streptomycin) and then placed in a 1.5-ml centrifuge tube containing digestion buffer (dispase II and collagenase IA, 1 mg/ml; Roche Applied Science).…”

Pentylenetetrazol-induced seizures strength in diabetic and normal serum glucose elevated male mice

“…In general, in glucose-excited neurons, glucose metabolism leads to KATP channel closure, triggering membrane depolarization, whereas in glucose-inhibited neurons, the inhibitory effect of elevated glucose is mediated by an ATP-independent K + channel. 30 Some studies have demonstrated that glucose-inhibited neurons have been found in some CNS regions, including NTS, DMV and hypothalamus. [30][31][32] The mechanism of glucoseinduced neuronal inhibition is not well understood.…”

“…30 Some studies have demonstrated that glucose-inhibited neurons have been found in some CNS regions, including NTS, DMV and hypothalamus. [30][31][32] The mechanism of glucoseinduced neuronal inhibition is not well understood. 38 In general, increased blood glucose level, possibly via aforesaid inhibitory mechanisms may have contributed to seizure severity reduction, although as said, details are less understood.…”