Electrophysiological characteristic of ATP-activated currents of trigeminal ganglion neurons with different diameter in rat / 中国应用生理学杂志

<p><b>AIM</b>To explore the characteristic of ATP-activated current in trigeminal ganglion (TG) neurons of rat.</p><p><b>METHODS</b>Whole-cell patch-clamp was performed.</p><p><b>RESULTS</b>(1) The majority (92.1%) of TG neurons responded to ATP applied externally with inward currents. We recorded three distinct ATP-activated currents: fast, slow and intermediate, which were concentration-dependent. (2) In general, the fast ATP-activated currents were distributed mainly in small-diameter TG neurons, the slow ATP-activated currents were distributed mainly in large-diameter TG neurons, and the intermediate ATP-activated currents were distributed mainly in intermediate-diameter TG neurons. (3) The time course of rising phase from 10% to 90% of the three distinct ATP-activated currents were as follows: fast: (33.6 +/- 4.5) ms; intermediate: (62.2 +/- 9.9) ms; slow: (302.1 +/- 62.0) ms, and that of desensitizing phase were (399.4 +/- 58.2) ms (fast), and > 500 ms (slow) respectively. (4) From the current-voltage relationship curves, it can be seen that the reversal potential values of the three distinct ATP-activated currents were the same, all being 0-5mV. And they all were characterized by inward rectification. (5) The dose-response curve for fast ATP-activated current shifted downwards as compared with the intermediate ATP-activated current, and that for the slow ATP-activated current shifted upwards.</p><p><b>CONCLUSION</b>The EC50s of the three curves tended to be identical. The results suggested that three kinds of distinct ATP-activated currents could be mediated by various subtypes of P2X receptors assembled by different subunits, and the subtypes existed in TG neurons of different diameters and transmit different information.</p>

The synergic effect of BK and ATP in peripheral nociceptive responses: an electrophysiological and behavioral study / 中华神经医学杂志

Objective To explore the responses and mechanisms of peripheral primary afferent neurons to adenosine 5'-triphosphate (ATP) and bradykinin (BK) applied separately or in combination by electrophysiological recording and behavioral observation. Methods The experiments were done on samples of acutely isolated rat dorsal root ganglion (DRG) neurons by the whole-cell patch clamp recording technique, to record ATP-activated current (IATP) and the regulating effect of BK on IATP and to observe the global behavior with pain behavioral experiment. Results ATP added after the pretreatment of BK in the majority of detected cells, IATP would be reinforced significantly, the degree of increment depending on the concentration of BK (BK 10-6 -10-4 mol/L), while the EC50 values of the concentration-response curve with and without pretreatment of BK were very close to each other (1.65×10-5 mol/L vs 2.0×10-5 mol/L). In the behavioral experiment, subcutaneously intraplantar injection of BK and ATP separately in hind limbs of rats both induced concentration-dependent pain behavioral (paw lifting) responses, while the duration of hindpaw lifting was prolonged dramatically with the increase in the ATP concentration, when BK (10-6 mol/L) was injected in combination with ATP (10-5, 10-4 and 10-3 mol/L). Conclusion Inflammatory mediators like BK and ATP etc play an important role in the production, transmission and modulation of pain information in peripheral sensory nerve endings. Both electrophysiological and behavioral experiments demonstrate that there is a synergic effect between ATP and BK, which is thought to be non-competitive. BK may reinforce IATP remarkably, and the pain responses induced by the increment in ATP concentration increase with the existence of BK.

Interaction of 5-HT2 and 5-HT3 receptor subtype in 5-HT-induced nociceptive responses in peripheral primary sensory nerve ending / 中国应用生理学杂志

<p><b>AIM</b>To study the correlation between 5-HT-induced pain response and the contribution by individual 5-HTR subtypes including 5-HT1R, 5-HT2R and 5-HT3R at the level of peripheral primary afferent.</p><p><b>METHODS</b>The experiments were done on acutely isolated trigeminal ganglion (TG) neurons using whole-cell patch clamp technique and the nociceptive effect was observed on behavior experiments by intraplantar injection of test drugs.</p><p><b>RESULTS</b>The majority of cells examined responded to 5-HT in a manner of concentration dependence (10(-6) - 10(-3) mol/) (61.4%, 54/88) and with a fast activating and rapid desensitizing inward current (I(5-HT)), which was thought to be mediated by the activation of 5-HT3R, since it could be blocked by 5-HT3R antagonist ICS 205930 and mimicked by 5-HT3R agonist 2-methyl-5-HT. It was found that I(5-HT) was potentiated by 5-HT2R agonist alpha-methyl-5-HT markedly, while 5-HT1R agonist R-(+)-UH 301 did not. In behavioral experiment performed on conscious rats, intraplantar injection of 5-HT(10(-5), 10(-4) and 10(-3) mol/L) induced an increment of cumulative lifting time first 20 min in a manner of concentration dependence. By dissociating 5-HTR subtypes using their corresponding antagonists (ICS and CYP) the potency order of hindpaw lifting time was identified as follows: 5-HT > 5-HT + ICS > 5-HT + CYP.</p><p><b>CONCLUSION</b>The results suggest that in 5-HT-induced nociceptive response at the primary sensory level 5-HT3R may play a role of initiation, but 5-HT2R mediates maintaining and modulatory effect in the processes of nociceptive information convey.</p>