Local anaesthetics block hyperpolarization-activated inward current in rat small dorsal root ganglion neurones

1 Hyperpolarizing voltage steps evoke slowly activating inward currents in a variety of neurones and in cardiac cells. This hyperpolarization-activated inward current (I-h) is thought to play a significant role in cell excitability, firing frequency, or in setting of the resting membrane potential in these cells. We studied the effects of lidocaine, mepivacaine, QX-314 and bupivacaine as well as its enantiomers on I-h in the membrane of dorsal root ganglion neurones (DRG). 2 The patch-clamp technique was applied to small dorsal root ganglion neurones identified in 200 muM thin slices of young rat DRGs. Under voltage-clamp conditions, the whole-cell I-h current was recorded in the presence of different concentrations of the local anaesthetics. In current-clamp mode the resting membrane potential and the voltage response of DRG neurones to injected current pulses were investigated. 3 I-h was reversibly blocked by bupivacaine, lidocaine and mepivacaine appliedexternally in clinically relevant concentrations. Concentration - response curves gave half-maximum inhibiting concentrations of 55, 99 and 190 muM, respectively. Bupivacaine block of the I-h current was not stereoselective. No significant effect was observed when QX-314 was applied to the external surface of the membrane. 4 In current-clamp experiments 60 muM bupivacaine slightly hyperpolarized the membrane. The membrane stimulation by low-amplitude current pulses in the presence of bupivacaine showed an increase of the hyperpolarizing responses. 5 Our findings suggest an important role of the I-h-block by local anaesthetics in the complex mechanism of drug action during epidural and spinal anaesthesia.