Effects of Bupivacaine and Ropivacaine on High-voltage–activated Calcium Currents of the Dorsal Horn Neurons in Newborn Rats

Abstract

BACKGROUND: Local anesthetics, such as bupivacaine, have been reported to block calcium currents in primary sensory neurons and to interfere with the release of neurotransmitters in central nervous system neurons. However, it is unknown whether local anesthetics affect the calcium current activity of central nervous system neurons. METHODS: Using a traditional whole cell voltage clamp technique, effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents (HVA-Ic(a)) were investigated in enzymatically dissociated dorsal horn neurons of neonatal rats. Calcium currents were evoked by testing pulses from a holding potential of -90 to 0 mV. RESULTS: Bupivacaine significantly reduced HVA-Ic(a) in a dose-dependent manner. The peak HVA-Ic(a) decreased by 24.5+/-2.5, 32.0+/-6.8, 59.4+/-6.2, 88.3+/-1.5, and 91.6+/-1.1% in response to 10, 30, 50, 100 and 200 microM bupivacaine, respectively. Unlike bupivacaine, ropivacaine markedly increased HVA-Ic(a) at lower concentrations (< 50 microM) but decreased HVA-Ic(a) at higher concentrations (> or = 50 microM). The percent increases in peak HVA-Ic(a) induced by 10 and 30 microM ropivacaine were 95+/-19.1 and 41.6+/-8.3%, respectively. The percent decreases in response to 50, 100, and 200 microM ropivacaine were 21.1+/-2.1, 63.2+/-6.0 and 79.1+/-7.6%, respectively. Results indicate that the inhibitory potency of ropivacaine on HVA-Ic(a) was significantly lower than that of bupivacaine at the same concentrations. CONCLUSIONS: The current study showed that bupivacaine inhibited HVA-Ic(a) recorded from dorsal horn neurons and that ropivacaine increased HVA-Ic(a) at lower concentrations but decreased HVA-Ic(a) at higher concentrations. The inhibitory potency of ropivacaine was lower than that of bupivacaine. Inhibition of calcium currents of central nervous system neurons may be related to the systemic neurotoxic effects of local anesthetics (e.g., convulsions, seizures).