Characteristics of ropivacaine block of Na+ channels in rat dorsal boot ganglion neurons

When used for epidural anesthesia, ropivacaine can produce a satisfactory s ensory block with a minor motor block. We investigated its effect on tetrod otoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na+ currents in rat dorsal root ganglion (DRG) neurons to elucidate the mechanisms underly ing the above effects. Whole-cell patch-clamp recordings were made from enz ymatically dissociated neurons from rat DRG. A TTX-S Na+ current was record ed preferentially from large DRG neurons and a TTX-R N+ current preferentia lly from small ones. Ropivacaine shifted the activation curve for the TTX-R Na+ channel in the depolarizing direction and the inactivation curve for b oth types of Na+ channel in the hyperpolarizing direction. Ropivacaine bloc ked TTX-S and TTX-R Na+ currents, but its half-maximum inhibitory concentra tion (IC50) was significantly lower for the latter current (116 +/- 35 vs 5 4 +/- 14 muM; P < 0.01); similar IC50 values were obtained with the (R)-iso mer of ropivacaine. Ropivacaine produced a use-dependent block of both type s of Na+ channels. Ropivacaine preferentially blocks TTX-R Na+ channels ove r TTX-S Na+ channels. We conclude that because TTX-R Na+ channels exist mai nly in small DRG neurons (which are responsible for nociceptive sensation), such selective action of ropivacaine could underlie the differential block observed during epidural anesthesia with this drug.