Effects of neomycin on high-threshold Ca(2+) currents and tetrodotoxin-resistant Na(+) currents in rat dorsal root ganglion neuron.
High-threshold Ca(2+) channels and tetrodotoxin-resistant Na(+) channels are highly expressed in small dorsal root ganglion neurons. In acutely isolated rat dorsal root ganglion neurons, the effects of neomycin, one of the aminoglycoside antibiotics, on high-threshold Ca(2+) currents and tetrodotoxin-resistant Na(+) currents were examined using whole-cell patch recording. We showed for the first time that neomycin dose-dependently inhibited peak high-threshold Ca(2+) currents and peak tetrodotoxin-resistant Na(+) currents with half-maximal inhibitory concentrations at 3.69 microM (n=20) and 1213.44 microM (n=25), respectively. Inactivation properties of high-threshold Ca(2+) currents and activation properties of tetrodotoxin-resistant Na(+) currents were also affected by neomycin with reduction of excitability of small dorsal root ganglion neurons. Half-maximal inactivation voltage of high-threshold Ca(2+) currents was -45.56 mV before and -50.46 mV after application of neomycin (n=10). Half-maximal activation voltage of tetrodotoxin-resistant Na(+) currents was -19.93 mV before and -11.19 mV after administration of neomycin (n=15). These results suggest that neomycin can inhibit high-threshold Ca(2+) currents and tetrodotoxin-resistant Na(+) currents in small dorsal root ganglion neurons, which may contribute to neomycin-induced peripheral and central analgesia.
Zhou
Yu
Y
Institute of Neurobiology, Fu-Dan University, 220 Han-Dan Road, Shanghai 20043 PR China.
Zhao
Zhi-Qi
ZQ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009355:Neomycin / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D015220:Calcium Channels; D015222:Sodium Channels; D013779:Tetrodotoxin; D009355:Neomycin