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PEDIATRIC ANESTHESIA

The Effects of Ropivacaine on Sodium Currents in Dorsal Horn Neurons of Neonatal Rats

Department of Anesthesiology, Shanghai First People‘s Hospital, Shanghai Medical University, Shanghai, China

We used a whole cell patch clamp technique to study the effects of ropivacaine on rat dorsal horn neurons. Under voltage clamp, ropivacaine (10–400 µM) produced a dose-dependent inhibition of sodium current. From a holding potential (V_h) of -80 mV, sodium currents evoked by test pulses to 0 mV were inhibited by ropivacaine with a mean drug concentration required to produce 50% current inhibition (IC₅₀) value of 117.3 µM, which was more than the value of the bupivacaine (IC₅₀ 53.7 µM). The inhibition effect of ropivacaine was also voltage-dependent. Current evoked from a V_h of -60 mV was inhibited by ropivacaine with a mean IC₅₀ value of 74.3 µM, which was less than that obtained at the V_h of -80 mV. The inhibition effect of ropivacaine on sodium current was use dependent. Repeated activation by a train of depolarizing pulses (5 Hz, 20 ms) increased the inhibitory effects of ropivacaine. The ratio amplitudes of the 20th to the first pulse were 91.2% and 71.1%, respectively, in the absence and presence of ropivacaine (50 µM). Ropivacaine also produced a significant hyperpolarizing shift of 11 mV in the steady-state inactivation curve of sodium current. The inhibition of ropivacaine on the sodium channel may contribute to the mechanism of action of local anesthetics during epidural and spinal anesthesia.

Implications: By using the whole-cell patch technique, ropivacaine is a voltage- and use-dependent inhibitor of the sodium current in dorsal horn neurons; it preferentially acts on steady-state inactivation by the sodium channel. The inhibition of ropivacaine on the sodium channel may contribute to the mechanism of action of local anesthetics during epidural and spinal anesthesia.

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