RT Journal Article
SR Electronic
T1 The aminoglycosides modulate the acid-sensing ionic-channel (ASIC) currents in dorsal-root ganglion neurons from the rat
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.109.152884
DO 10.1124/jpet.109.152884
A1 Anibal Garza
A1 Omar Lopez-Ramirez
A1 Rosario Vega
A1 Enrique Soto
YR 2009
UL http://jpet.aspetjournals.org/content/early/2009/10/28/jpet.109.152884.abstract
AB 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 μM) 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 μM) 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 μM) produced a significant reduction in the amplitude of the proton-gated current. Neomycin and gentamycin had no significant action. Reduction of extracellular Ca2+ 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.The American Society for Pharmacology and Experimental Therapeutics