Local anesthetic inhibition of voltage-activated potassium currents in ratdorsal root ganglion neurons

Background: Local anesthetic actions on the K+ channels of dorsal root gang lion (DRG) and dorsal horn neurons may modulate sensory blockade during neu raxial anesthesia. In dorsal horn neurons, local anesthetics are known to i nhibit transient but not sustained K+ currents. The authors characterized t he effects of local anesthetics on K+ currents of isolated DRG neurons. Methods: The effects of lidocaine, bupivacaine, and tetracaine on K+ curren ts in isolated rat DRG neurons were measured with use of a whole cell patch clamp method. The currents measured were fast-inactivating transient curre nt (I-Af), slow-inactivating transient current (I-As), and noninactivating sustained current (I-Kn). Results: One group of cells (type 1) expressed I-Af and I-Kn. The other gro up (type 2) expressed I-As and I-Kn The diameter of type 2 cells was smalle r than that of type 1 cells. Lidocaine and bupivacaine inhibited all three K+ currents. Tetracaine inhibited I-As and I-Kn but not I-Af. For bupivacai ne, the concentration for half-maximal inhibition (IC50) of I-Kn type 2 cel ls was lower than that for I-Kn in type 1 cells (57 vs. 121 muM) Similar re sults were obtained for tetracaine (0.6 us. 1.9 mM) and for lidocaine (2.2 us. 5.1 mM). Conclusions: Local anesthetics inhibited both transient and sustained K+ cu rrents in DRG neurons. Because K+ current inhibition is known to potentiate local anesthetic-induced impulse inhibition, the lower IC50 for I-Kn of sm all type 2 cells may reflect preferential inhibition of impulses in nocicep tive neurons. The overall modulatory actions of local anesthetics probably are determined by their differential effects on presynaptic (DRG) and posts ynaptic (dorsal horn neurons) K+ currents.