Inhibition of acid-sensing ion channels by levo-tetrahydropalmatine in rat dorsal root ganglion neurons

2014 ◽  
Vol 93 (2) ◽  
pp. 333-339 ◽  
Author(s):  
Ting-Ting Liu ◽  
Zu-Wei Qu ◽  
Chun-Yu Qiu ◽  
Fang Qiu ◽  
Cuixia Ren ◽  
...  
Keyword(s):  
Ion Channels ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Acid Sensing Ion Channels ◽  
Ganglion Neurons

scholarly journals Sa12b Peptide from Solitary Wasp Inhibits ASIC Currents in Rat Dorsal Root Ganglion Neurons

Toxins ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 585 ◽  
Author(s):  
Hernández ◽  
Konno ◽  
Salceda ◽  
Vega ◽  
Zaharenko ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Inhibitory Effect ◽  
Dorsal Root Ganglion Neurons ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Drg Neurons ◽  
Concentration Dependent Manner ◽  
Acid Sensing Ion Channels ◽  
Ganglion Neurons

In this work, we evaluate the effect of two peptides Sa12b (EDVDHVFLRF) and Sh5b (DVDHVFLRF-NH2) on Acid-Sensing Ion Channels (ASIC). These peptides were purified from the venom of solitary wasps Sphex argentatus argentatus and Isodontia harmandi, respectively. Voltage clamp recordings of ASIC currents were performed in whole cell configuration in primary culture of dorsal root ganglion (DRG) neurons from (P7-P10) CII Long-Evans rats. The peptides were applied by preincubation for 25 s (20 s in pH 7.4 solution and 5 s in pH 6.1 solution) or by co-application (5 s in pH 6.1 solution). Sa12b inhibits ASIC current with an IC50 of 81 nM, in a concentration-dependent manner when preincubation application was used. While Sh5b did not show consistent results having both excitatory and inhibitory effects on the maximum ASIC currents, its complex effect suggests that it presents a selective action on some ASIC subunits. Despite the similarity in their sequences, the action of these peptides differs significantly. Sa12b is the first discovered wasp peptide with a significant ASIC inhibitory effect.

Novel Mechanism of Inhibition by the P2 Receptor Antagonist PPADS of ATP-Activated Current in Dorsal Root Ganglion Neurons

2000 ◽  
Vol 83 (5) ◽  
pp. 2533-2541 ◽  
Author(s):  
Chaoying Li
Keyword(s):  
Ion Channels ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Disulfonic Acid ◽  
Slow Phase ◽  
Maximal Response ◽  
Dependent Manner ◽  
Ganglion Neurons ◽  
Gated Ion Channels

The antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) has been proposed to selectively antagonize the actions of ATP at P2X receptors. Whole cell patch-clamp recording techniques therefore were used to characterize PPADS inhibition of ATP-activated current in bullfrog dorsal root ganglion (DRG) neurons. PPADS, 0.5–10 μM, inhibited ATP-activated current in a concentration-dependent manner with an IC50 of 2.5 ± 0.03 μM. PPADS produced a gradual decline of ATP-activated current to a steady state, but this was not an indication of use dependence as the gradual declining component could be eliminated by exposure to PPADS before ATP application. In addition, ATP-activated current recovered completely from inhibition by PPADS in the absence of agonist. The slow onset of inhibition by PPADS was not apparently due to an action at an intracellular site as inclusion of 10 μM PPADS in the recording pipette neither affected the ATP response nor did it alter inhibition of the ATP response when 2.5 μM PPADS was applied externally. PPADS, 2.5 μM, decreased the maximal response to ATP by 51% without changing its EC50. PPADS inhibition of ATP-activated current was independent of membrane potential between −80 and +40 mV and did not involve a shift in the reversal potential of the current. The magnitude of PPADS inhibition of ATP-activated current was dependent on the duration of the prior exposure to PPADS. The time constants of both onset and offset of PPADS inhibition of ATP-activated current did not differ significantly with changes in ATP concentration from 1 to 5 μM. Recovery of ATP-activated current from PPADS inhibition also exhibited a slow phase that was not accelerated by the presence of agonist and was dependent on the concentration of PPADS. The apparent dissociation rate of PPADS from unliganded ATP-gated ion channels was much greater than the rate of the slow phase of recovery of ATP-activated current from PPADS inhibition. The results suggest that PPADS can inhibit P2X receptor function in a complex noncompetitive manner. PPADS produces a long-lasting inhibition that does not appear to result from open channel block but rather from an action at an allosteric site apparently accessible from the extracellular environment that involves a greatly reduced rate of dissociation from liganded versus unliganded ATP-gated ion channels.

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