| Title | The aminoglycosides modulate the acid-sensing ionic-channel (ASIC) currents in dorsal-root ganglion neurons from the rat. | | Author(s) | Garza A, Lopez-Ramirez O, Vega R, Soto E | | Institution | 1 Instituto de Fisiologia, Benemerita Universidad Autonoma de Puebla, Mexico; | | Source | J Pharmacol Exp Ther 2009 Oct 28. | | Abstract | Acid-sensing ionic channels (ASICs) have been shown to have a significant role in a growing number of physiological and pathological processes, such as nociception, synaptic transmission and plasticity, mechano-sensation and acidosis-induced neuronal injury. The discovery of pharmacological agents targeting ASICs has significant therapeutic potential and use as a research tool. In our work, we studied the action of transient perfusion (5 to 15 s) of aminoglycosides (AGs) (streptomycin and neomycin) on the proton-gated ionic currents in dorsal root ganglion neurons (DRG) of the rat and in HEK-293 cells. In DRG neurons, streptomycin and neomycin (30 muM) produced a significant, concentration-dependent and reversible reduction in the amplitude of the proton-gated current, and a slowing of the desensitization rate of the ASIC current. Gentamycin (30 muM) also showed a significant reversible action on the ASIC currents. The curves of the pH-effect for streptomycin and neomycin indicated that their effect was not significantly affected by pH. In HEK-293 cells, streptomycin (30 muM) produced a significant reduction in the amplitude of the proton-gated current. Neomycin and gentamycin had no significant action. Reduction of extracellular Ca(2+) concentration produced a significant increase in the action of streptomycin and neomycin on the desensitization time-course of ASIC currents. These results indicate that ASICs are molecular targets for AGs, which may contribute to the understanding of their actions on excitable cells. Moreover, AGs may constitute a source to develop novel molecules with a greater affinity, specificity and selectivity for the different ASIC subunits. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19864615 |
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