[Midazolam presynaptically inhibits excitatory synaptic transmission in the superficial dorsal horn of the rat spinal cord].
Whole-cell voltage-clamp recordings were made from superficial dorsal horn neurons in thin slices of neonatal rat spinal cord. Spontaneously occurring glutaminergic miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presence of tetrodotoxin, strychnine and bicuculline. Bath-application of midazolam (5-60 microM) reduced the frequency of mEPSCs dose-dependently and this depression was antagonized by flumazenil 15 microM. In 8 neurons studied, midazolam 15 microM affected neither the amplitude profiles nor the mean amplitudes of the mEPSCs, suggesting a presynaptic site of action. In a nominally Ca(2+)-free solution, midazolam still reduced the frequency of mEPSCs, but to a lesser extent than in a standard solution. We conclude that midazolam may presynaptically inhibit excitatory synaptic transmission in the superficial dorsal horn by affecting both Ca2+ entry into the nerve terminals and transmitter release mechanisms downstream to Ca2+ entry.
Hanzawa
S
S
Second Department of Anesthesiology, Dokkyo University School of Medicine, Tochigi.
D000759:Adjuvants, Anesthesia / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D008874:Midazolam / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D000759:Adjuvants, Anesthesia; D014151:Anti-Anxiety Agents; D008874:Midazolam; D002118:Calcium