Local Anesthetic Inhibition of Voltage-activated Potassium Currents in Rat Dorsal Root Ganglion Neurons

2001 ◽  
Vol 94 (6) ◽  
pp. 1089-1095 ◽  
Author(s):  
Hirochika Komai ◽  
Thomas S. McDowell
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Dorsal Root ◽  
Drg Neurons ◽  
Dorsal Horn Neurons ◽  
K Currents

Background Local anesthetic actions on the K+ channels of dorsal root ganglion (DRG) and dorsal horn neurons may modulate sensory blockade during neuraxial anesthesia. In dorsal horn neurons, local anesthetics are known to inhibit transient but not sustained K+ currents. The authors characterized the effects of local anesthetics on K+ currents of isolated DRG neurons. Methods The effects of lidocaine, bupivacaine, and tetracaine on K+ currents in isolated rat DRG neurons were measured with use of a whole cell patch clamp method. The currents measured were fast-inactivating transient current (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 group (type 2) expressed I(As) and I(Kn). The diameter of type 2 cells was smaller 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 bupivacaine, the concentration for half-maximal inhibition (IC50) of I(Kn) in type 2 cells was lower than that for I(Kn) in type 1 cells (57 vs. 121 microM). Similar results were obtained for tetracaine (0.6 vs. 1.9 mM) and for lidocaine (2.2 vs. 5.1 mM). Conclusions Local anesthetics inhibited both transient and sustained K+ currents in DRG neurons. Because K+ current inhibition is known to potentiate local anesthetic-induced impulse inhibition, the lower IC50 for I(Kn) of small type 2 cells may reflect preferential inhibition of impulses in nociceptive neurons. The overall modulatory actions of local anesthetics probably are determined by their differential effects on presynaptic (DRG) and postsynaptic (dorsal horn neurons) K+ currents.

Glutamate-mediated slow synaptic currents in neonatal rat deep dorsal horn neurons in vitro

1996 ◽  
Vol 76 (3) ◽  
pp. 1465-1476 ◽  
Author(s):  
B. A. Miller ◽  
C. J. Woolf
Keyword(s):  
Dorsal Horn ◽  
Slow Component ◽  
Small Diameter ◽  
Primary Afferents ◽  
Neonatal Rat ◽  
Dorsal Horn Neurons ◽  
Stimulation Of

1. The role of glutamate in slow excitatory synaptic transmission between small-diameter primary afferents and deep dorsal horn neurons was examined in neonatal rat spinal cord in vitro with the use of the whole cell voltage-clamp technique. 2. Single-shock electrical stimulation of large-diameter A beta-fibers evoked a short-latency (< 10 ms) fast (< 500 ms) excitatory postsynaptic current (EPSC). Stimulation of small-diameter A delta- and C fibers resulted, in addition, in a slowly rising and decaying EPSC (lasting up to 14 s) following the fast EPSC. The slow EPSC was never observed with stimulation of A beta-fibers. 3. Two patterns of EPSCs were observed, "type 1" and "type 2," which differed in their time course (lasting up to 1 and 14 s, respectively). The type 1 response was biphasic, with a fast monosynaptic component followed by an invariant, presumably monosynaptic, late slow component. The type 2 response was multiphasic, with a fast monosynaptic component followed by a slow component composed of fast polysynaptic currents superimposed on a slow current. 4. The fast monosynaptic component had a linear conductance, whereas the late slower component of the A beta-fiber-evoked response had a negative slope conductance at holding potentials more negative than -23 mV. Both currents reversed at a membrane potential of -1.2 +/- 2.8 (SE) mV. 5. With the use of selective non-N-methyl-D-aspartate (non-NMDA) and NMDA receptor antagonists [6-cyano-7-nitroquinox-aline-2,3-dione (CNQX) or 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo (F) quinoxaline and D(-)-2-amino-5-phosphonopentanoic acid (D-AP5), respectively] we showed that both the early fast (A beta-fiber evoked) and the late slow (A delta- and C fiber evoked) components were mediated by non-NMDA and NMDA receptors. CNQX suppressed both the early fast and late slow components of the compound EPSC, whereas D-AP5 suppressed the polysynaptic currents of the early fast component and the late slow component without significantly affecting the early fast monosynaptic component. 6. Slow EPSCs summated on low-frequency (1 or 10 Hz), repetitive stimulation and produced long-duration "tail" currents on cessation of the stimulus. The amount of temporal summation was proportional to the duration of the slow EPSC and the frequency of stimulation. 7. Our results suggest that slow ionotropic-glutamate-receptor-mediated EPSCs produced by the stimulation of small-diameter primary afferents play an important role in activity-dependent synaptic plasticity in the dorsal horn.

Blockade of Na+and K+Currents by Local Anesthetics in the Dorsal Horn Neurons of the Spinal Cord 

1998 ◽  
Vol 88 (1) ◽  
pp. 172-179 ◽  
Author(s):  
Andrea Olschewski ◽  
Gunter Hempelmann ◽  
Werner Vogel ◽  
Boris V. Safronov
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Epidural Anesthesia ◽  
Local Anesthetics ◽  
Molecular Mechanisms ◽  
K Channel ◽  
Delayed Rectifier ◽  
Patch Clamp Technique ◽  
Dorsal Horn Neurons ◽  
K Currents

Background The dorsal horn of the spinal cord is a pivotal point for transmission of neuronal pain. During spinal and epidural anesthesia, the neurons of the dorsal horn are exposed to local anesthetics. Unfortunately, little is known about the action of local anesthetics on the major ionic conductances in dorsal horn neurons. In this article, the authors describe the effects of bupivacaine, lidocaine, and mepivacaine on voltage-gated Na+ and K+ currents in the membranes of these neurons. Methods The patch-clamp technique was applied to intact dorsal horn neurons from laminae I-III identified in 200-microm slices of spinal cord from newborn rats. Under voltage-clamp conditions, the whole-cell Na+ and K+ currents activated by depolarization were recorded in the presence of different concentrations of local anesthetics. Results Externally applied bupivacaine, lidocaine, and mepivacaine produced tonic block of Na+ currents with different potencies. Half-maximum inhibiting concentrations (IC50) were 26, 112, and 324 microM, respectively. All local anesthetics investigated also showed a phasic, that is, a use-dependent, block of Na+ channels. Rapidly inactivating K+ currents (KA currents) also were sensitive to the blockers with IC50 values for tonic blocks of 109, 163, and 236 microM, respectively. The block of KA currents was not use dependent. In contrast to Na+ and KA currents, delayed-rectifier K+ currents were almost insensitive to the local anesthetics applied. Conclusions In clinically relevant concentrations, local anesthetics block Na+ and KA currents but not delayed-rectifier K+ currents in spinal dorsal horn neurons. The molecular mechanisms of Na+ and K+ channel block by local anesthetics seem to be different. Characterization of these mechanisms could be an important step in understanding the complexity of local anesthetic action during spinal and epidural anesthesia.

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