Desheathed Rabbit Vagus Research Articles

Hyperpolarizing afterpotentials in C fibers and local anesthetic effects of clonidine and lidocaine.

Effects of clonidine and lidocaine on the hyperpolarizing after-potential (HAP) and frequency-dependent block in C fibers were examined on desheathed rabbit vagus nerves, using the sucrose gap technique. A single action potential (AP) was followed by a fast and a slow HAP. Clonidine, at concentrations from 0.05 to 50 mumol/l, decreased the fast HAP, while the AP amplitude was unchanged. At a 500 mumol/l concentration of clonidine, the fast HAP amplitude was similar to control, the slow HAP was increased, and the AP amplitude decreased. Lidocaine at 500 mumol/l delayed and broadened the HAP, making a distinction between fast and slow HAP impossible, and decreased and delayed the AP amplitude. In the presence of lidocaine (500 mumol/l), clonidine at concentrations from 0.05 to 500 mumol/l decreased the HAP amplitude, without modifying the lidocaine-induced shape of the HAP. The modifications of the HAP, however, do not contribute to the local anesthetic effects of clonidine, as the addition of clonidine (0.5 and 500 mumol/l) to Locke or lidocaine (500 mumol/l) solution does not enhance the frequency-dependent block (3 and 10 Hz) observed with either Locke or lidocaine solution alone.

Clonidine enhances the effects of lidocaine on C-fiber action potential.

We examined local anesthetic effects of clonidine and its interaction with lidocaine with regard to tonic inhibition of the C-fiber action potential (AP) on the isolated, desheathed rabbit vagus nerve by the sucrose gap method. Clonidine and lidocaine at 500 microM concentrations caused a comparable degree of C-fiber inhibition, corresponding to an AP area under the curve of 75.8% +/- 9.4% (mean +/- SE) and 82.2% +/- 5.9% of control, respectively. Concentrations of clonidine less than 500 microM did not inhibit C-fiber AP. Clonidine, added in concentrations of 500 nM, 500 microM, and 5 mM to a 500 microM lidocaine perfusion, caused a significant decrease in fiber blockade of 18%, 20%, and 54%, respectively, as compared with clonidine added to Locke perfusion (P less than 0.05). The sodium channel blocker tetrodotoxin (3 microM) decreased the AP area to 9.3% +/- 1.3% of control. The remaining tetrodotoxin-resistant AP was almost completely blocked by clonidine (500 microM) and lidocaine (500 microM), indicating a higher susceptibility of tetrodotoxin-resistant fibers to the two drugs than the C-fiber population as a whole. The enhancing effect of a low dose of clonidine (500 nM) on lidocaine-induced (500 microM) inhibition of C-fiber AP might explain the clinical observation that clonidine, at approximately 1000-fold lower concentrations than lidocaine, prolongs the action of lidocaine in peripheral nerve block.

After potentials in nonmyelinated nerve fibers

1. The sucrose-gap technique was employed to examine the different types of after potentials that follow, in desheathed rabbit vagus nerves, a single action potential (AP) elicited by a short (0.4 ms) supramaximal depolarizing pulse. 2. A fast and a slow hyperpolarizing after potential (fHAP and sHAP) as well as a depolarizing after potential (DAP) followed a single spike. Both the fHAP and the sHAP showed a dependence on the K+ electrochemical gradient, indicating that they are due to an outwardly oriented current of K+ ions. 3. The fHAP was sensitive to low concentrations of tetraethylammonium (TEA; 1 mM) and 4-aminopyridine (4-AP; 10 microM) and to millimolar concentrations of Ba2+. We conclude that the fHAP reflects the tail of the delayed rectifier K+ current. 4. The sHAP contained a Ca(2+)-sensitive component that showed a requirement for voltage-dependent Ca2+ entry during the AP. This component was completely blocked by low concentration of TEA (1 mM) and by Cd2+ (1 mM), but unaffected by 4-AP. These observations suggest that it reflects a current flowing through Ca(2+)-activated K+ channels. The remaining, apparently Ca(2+)-insensitive, component was insensitive to 4-AP and could be blocked by TEA only at concentrations greater than 50 mM. 5. The DAP usually appeared when the external concentration of K+ was increased to above approximately 8 mM, but sometimes it was clearly visible even at lower [K+]o. The DAP was TEA insensitive and entirely Ca2+ dependent. This latter property is inconsistent with the widely accepted hypothesis according to which the DAP reflect the accumulation of K+ in the extracellular space during the AP. 6. The origins of both the Ca(2+)-insensitive component of the sHAP and the DAP are not clear. However, in view of the fact that the sucrose-gap technique records not only the membrane potential of the nerve fibers but also of the surrounding glia, there is the possibility that these after potentials reflect changes in the electrical properties of the satellite Schwann cells.

Acute Progesterone Treatment Has No Effect on Bupivacaine-Induced Conduction Blockade in the Isolated Rabbit Vagus Nerve

Pregnancy decreases anesthetic requirements during regional anesthesia. Using an in vitro animal model, this study attempts to elucidate the mechanism of hormonal effects on nerve conduction in desheathed rabbit vagus nerve. The acute effects of progesterone administration on neural blockade induced by bupivacaine were investigated in terms of changes in compound action potentials of A, B, and C fibers. No change in baseline compound action potential was found after 30 min of perfusion of the nerve with progesterone. Exposure of the nerve to progesterone before exposure to bupivacaine did not significantly increase the degree of conduction blockade produced by bupivacaine, and a radioactive assay demonstrated that progesterone was taken up acutely by neural tissue over a 45-min measurement period. These results indicate that although progesterone was taken up in significant amounts by neural tissue, an acute exposure does not increase the sensitivity of the nerves to bupivacaine. Hence, the increased sensitivity of nerves to local anesthetics seen with pregnancy or with chronic progesterone treatment requires some period of time to occur. The mechanism is therefore unlikely to be a direct effect of progesterone on the cell membrane but may involve hormonal effects on protein synthesis.

Decreased Incidence of Tourniquet Pain During Spinal Anesthesia with Bupivacaine

In a previous report, the incidence of tourniquet pain was found to be 25% with bupivacaine and 60% with tetracaine (P less than 0.05) spinal anesthesia. On the other hand, tetracaine is more potent than bupivacaine in abolishing the single-compound action potential in vitro in isolated nerves. These conflicting observations may be reconciled if bupivacaine produced greater frequency-dependent conduction blockade of nerve action potentials. This hypothesis was tested in C fibers of isolated, desheathed rabbit vagus nerves. The nerves were supramaximally stimulated at frequencies of 9 or 15 Hz. After a control period, the nerves were exposed to bupivacaine (0.2 mM) or tetracaine (0.02 mM) for 30 minutes. The local anesthetics were then washed out by continuous constant-rate perfusion. The decline and recovery of the first and last action potential amplitudes of the train were measured. Bupivacaine and tetracaine produced similar depression of the first action potential of the 9-Hz and 15-Hz trains. However, bupivacaine caused a delayed recovery of the last action potential of the 15-Hz train but not of the 9-Hz train. These results show that bupivacaine produces greater frequency-dependent conduction blockade of C fibers than does tetracaine. These findings offer a possible explanation as to why spinal anesthesia with bupivacaine results in a lower incidence of tourniquet pain than tetracaine.

Decreased Incidence of Tourniquet Pain during Spinal Anesthesia with Bupivacaine A Possible Explanation

In a previous report, the incidence of tourniquet pain was found to be 25% with bupivacaine and 60% with tetracaine (P < 0.05) spinal anesthesia. On the other hand, tetracaine is more potent than bupivacaine in abolishing the single-compound action potential in vitro in isolated nerves. These conflicting observations may be reconciled if bupivacaine produced greater frequency-dependent conduction blockade of nerve action potentials. This hypothesis was tested in C fibers of isolated, desheathed rabbit vagus nerves. The nerves were supramaximally stimulated at frequencies of 9 or 15 Hz. After a control period, the nerves were exposed to bupivacaine (0.2 mM) or tetracaine (0.02 mM) for 30 minutes. The local anesthetics were then washed out by continuous constant-rate perfusion. The decline and recovery of the first and last action potential amplitudes of the train were measured. Bupivacaine and tetracaine produced similar depression of the first action potential of the 9-Hz and 15-Hz trains. However, bupivacaine caused a delayed recovery of the last action potential of the 15-Hz train but not of the 9-Hz train. These results show that bupivacaine produces greater frequency-dependent conduction blockade of C fibers than does tetracaine. These findings offer a possible explanation as to why spinal anesthesia with bupivacaine results in a lower incidence of tourniquet pain than tetracaine.

Calcium efflux and intracellular exchangeable calcium in mammalian nonmyelinated nerve fibers

Calcium efflux was measured in desheathed rabbit vagus nerves loaded with 45Ca2+. The effects of extracellular calcium, sodium, phosphate, potassium and lanthanum ions on the calcium efflux were investigated and the distribution of intracellular calcium determined by kinetic analysis of 45Ca2+ efflux profiles. The 45Ca2+ desaturation curve can be adequately described by three exponential terms. The rate constant of the first component (0.2 min-1) corresponds to an efflux from an extracellular compartment. The two slow components had rate constants of 0.03 and 0.08 min-1 and represent the efflux from two intracellular pools. The amounts of exchangeable calcium in these two pools, after a loading period of 150 min, were 0.170 and 0.102 mmol/kg wet weight, respectively. The total calcium efflux in physiological conditions amounted to about 24 fmol cm-2 sec-1. The magnitude of the two intracellular compartments as well as the total calcium efflux were markedly affected by extracellular phosphate, sodium and lanthanum, whereas the corresponding rate constants remained almost unchanged. Phosphate reversed the effect of sodium withdrawal on the calcium efflux: in the absence of phosphate, sodium withdrawal increased the calcium efflux to 224%, but in the presence of phosphate, sodium withdrawal decreased calcium efflux to 44%. Phosphate also affected the increase in calcium efflux produced by inhibitors of mitochondrial calcium uptake, suggesting that two different mitochondrial pools contribute to the control and regulation of intracellular calcium and of the transmembrane calcium transport.

Effects of Fentanyl and Sufentanil on Peripheral Mammalian Nerves

The effects of fentanyl and sufentanil on peripheral nerves were evaluated in isolated sheathed and desheathed rabbit vagus nerves. The action potential amplitudes of A and C fibers were recorded before and after a 30-min exposure to 50 and 100 micrograms/ml of fentanyl and sufentanil. A reversible decrease in the action potential amplitude of A fibers in desheathed nerves was observed after exposure to 100 micrograms/ml of each drug. The action potential amplitude of C fibers was also decreased but not to the same degree as was the A fiber action potential. Pretreatment with naloxone failed to block the reduction in action potential amplitude produced by the two opiates. No evidence of irreversible conduction blockade indicative of local neural toxicity was seen in these studies. The results suggest that high concentrations of fentanyl and sufentanil may exert a weak local anesthetic-type action on peripheral nerves.

Release of adenosine, inosine and hypoxanthine from rabbit non-myelinated nerve fibres at rest and during activity.

The composition of the efflux from desheathed rabbit vagus nerve, loaded with radioactivity by incubation in [3H]adenosine, was studied at rest and during electrical activity and after application of inhibitors of ecto-enzymes and modifications of intermediary metabolism. In addition, the degradation of externally applied ATP and adenosine was examined. [3H]ATP applied to the incubation medium was degraded to ADP, AMP, adenosine and inosine. The hydrolysis to nucleosides was inhibited by alpha, beta-methylene ADP; the appearance of AMP and nucleosides was slowed by beta, gamma-methylene ATP. Deamination of [3H]adenosine was blocked by 2-deoxycoformycin. The effluent from resting and stimulated preparations showed the presence of large amounts of inosine and hypoxanthine, smaller amounts of adenosine and adenine and traces of nucleotides. The composition of the effluent was not significantly altered by addition of alpha, beta-methylene ADP; beta, gamma-methylene ATP or 2-deoxycoformycin. Application of glucose-free solutions caused a large release of adenosine instead of inosine and hypoxanthine and a small increase in resting and stimulated efflux of 3H. Addition of 2-deoxyglucose produced a large increase in resting efflux and increased liberation of adenosine. Cyanide, 2,4-dinitrophenol, arsenate or salicylate increased the resting efflux of adenosine, inosine and hypoxanthine, and the effect of activity. It is concluded that electrical activity leads to release of adenosine, inosine and hypoxanthine, in various proportions depending on metabolic state, and that there is practically no liberation of nucleotides from nerve axons.

Involvement of intracellular calcium in the phosphate efflux from mammalian nonmyelinated nerve fibers.

Phosphate efflux was measured as the fractional rate of loss of radioactivity from desheathed rabbit vagus nerves after loading with radiophosphate . The effects of strategies designed to increase intracellular calcium were investigated. At the same time, the exchangeable calcium content was measured using 45Ca. Application of calcium ionophore A23187 increased phosphate efflux in the presence of external calcium in parallel with an increase in calcium content. In the absence of external calcium, there was only a late, small increase in phosphate efflux. For nerves already treated with the calcium ionophore, the phosphate efflux was sensitive to small changes in external calcium, in the range 0.2 to 2 mM calcium, whereas similar increases in calcium in absence of ionophore gave much smaller increases in phosphate efflux. Removal of external sodium (choline substitution) produced an initial increase in phosphate efflux followed by a fall. The initial increase in phosphate efflux was much larger in the presence of calcium, than in its absence. The difference was again paralleled by an increase in calcium content of the preparation, thought to be due to inhibition of Na/Ca exchange by removal of external sodium. Measurements of ATP content and ATP, ADP, phosphate and creatine phosphate ratios did not indicate significant metabolic changes when the calcium content was increased. Stimulation of phosphate efflux by an increase in intracellular calcium may be due to stimulation of phospholipid metabolism. Alternatively, it is suggested that stimulation of phosphate efflux is associated with the stimulation of calcium efflux, possibly by cotransport of calcium and phosphate.

Differential Sensitivity of Fast and Slow Fibers in Mammalian Nerve II. Margin of Safety for Nerve Transmission

In a previous study it was found that concentrations of local anesthetics required to block large, fast-conducting nerve fibers were lower than those required to block small, slow-conducting fibers. The present study was instituted to evaluate the margin of safety for transmission in large versus small nerve fibers, the margin of safety being defined as the ratio between the magnitude of the action potential and the magnitude of the critical membrane potential. The effect of reducing the sodium-activating current, which reduces the magnitude of the action potential by sodium deficient solutions and tetrodotoxin application to the desheathed rabbit vagus nerve trunk (in vitro), was examined. Anode block (another method of reducing sodium current) is also discussed. In all instances, the margin of safety for transmission was greater in small, slow fibers than in large, fast fibers. The variations seen in nerve response to tetrodotoxin application are explained by the presence of nerve fiber diffusion barriers; the large fibers show more diffusion protection than the small fibers. Onset, duration, and intensity of differential nerve blockade by drugs reflect a balance between diffusion barriers and axon membrane sensitivity.

Release of inorganic phosphate during activity in mammalian non-myelinated nerve fibres.

1. The efflux of labelled phosphate was measured in desheathed rabbit vagus nerve at rest and during activity.2. In solutions with 2 mM-phosphate and 1 mM-K the rate constant of the resting efflux was 2.7 x 10(-3) min(-1); stimulation caused an extra fractional loss of 2.8 x 10(-6) impulse(-1).3. Lowering the phosphate concentration decreased the resting and the stimulated efflux; with 0.2 mM-phosphate the corresponding values were 1.9 x 10(-3) min(-1) and 1.8 x 10(-6) impulse(-1), respectively.4. Increasing the K to 5.6 mM decreased both resting and stimulated efflux.5. Lowering the temperature decreased the resting efflux with a Q(10) of 2.9 and the stimulated efflux with a Q(10) of 8.1.6. Chromatography of the effluent showed that at rest and during activity at least 96% of the radiophosphate was in the orthophosphate fraction.7. Replacing the Na of the solution by Li lowered the rate constant of the resting efflux to 0.8 x 10(-3) min(-1) and abolished the extra release during activity, without reduction of the action potential.8. The presence of ouabain did not affect the resting efflux, except at 100 muM, when a transient reduction was found. The extra fractional loss was not affected with 0.001 muM; with 0.01-0.5 muM, it was reduced without much change in the action potential, and abolished at higher concentrations.9. The results agree with the hypothesis that the extra release results from an increase in internal inorganic phosphate caused by increased break-down of ATP during recovery.10. Comparison with the O(2) consumption shows that about 1% of the inorganic phosphate liberated at the inside of the axons escapes to the outside.

Oxygen consumption and phosphate efflux in mammalian non-myelinated nerve fibres.

1. A comparison has been made between the efflux of labelled phosphate from the non-myelinated fibres of the desheathed rabbit vagus nerve at 37 degrees C and the corresponding O2 consumption at rest and during activity, and during a variety of experimental interventions. 2. The resting rate constant of phosphate efflux was 2.61 X 10(-3) min-1: electrical stimulation (10 sec-1, 3 min) produced an extra fractional loss of 6.75 X 10(-6) impulse-1. 3. The corresponding resting O2 consumption was 0.484 m-mole x kg-1 impulse-1. 4. Ouabain (100 microM) produced a sustained depression (of about 40%) of the resting O2 consumption, accompanied by a transient fall (of about 14%) in the rate constant of phosphate efflux. 5. Na salicylate (10 mM) or Na arsenate (1 mM) produced a much larger increase in phosphate efflux than in resting O2 consumption. 6. Changing the external phosphate concentration (between 0.02 and 2 mM), addition of acetylcholine (1.7 mM), and addition of lanthanum (20 microM)--all of which are known to affect markedly the phosphate efflux in rabbit non-myelinated fibres--had little or no effect on the resting O2 consumption or, where tested, on the extra O2 consumption with electrical stimulation. 7. Changing the external Ca concentration (between 0.09 and 9 mM) had only minor effects on the O2 consumption (resting and stimulated) and on the rate constant of resting phosphate efflux. 8. It is concluded that although changes in metabolism of the nerve produce changes in the phosphate efflux expected on the basis of the concomitant changes in the internal concentration of inorganic phosphate, the converse is not true; and increases and decreases in the rate constant of phosphate efflux do not necessarily signal the corresponding metabolic changes.

Observations on the mechanism for the active extrusion of lithium in mammalian non-myelinated nerve fibres.

1. A study has been made of the O2 consumption, and the corresponding efflux of labelled phosphate, from the non-myelinated fibres of the desheathed rabbit vagus nerve at 37 degrees C in Locke solutions in which various ions were substituted for Na, and also in the presence of ouabain. 2. Switching from Na-Locke solution to Li-Locke solution produced a small transient decrease in the resting O2 consumption (of 14%), which rapidly recovered to its original value. This was accompanied by an initial brief rise followed by a maintained fall in the resting phosphate efflux. 3. In Li-Locke solution, ouabain (100 microM) produced a fall in the resting O2 consumption of 40%, i.e. similar to that produced in Na-Locke solution. Any depression of the resting phosphate efflux was absent or small. 4. In choline-Locke solution, in Tris-Locke solution, in K-Locke solution or in sucrose-Locke solution the resting O2 consumption, which fell by 30-40%, was insensitive to the addition of ouabain (100 microM). 5. Addition of either Na ions or of Li ions partially restored respiration in choline-Locke solution, Li being an order of magnitude less effective than Na. 6. In choline-Locke solution the internal K content was not affected by ouabain. However, if Li (77 mM) was present in the bathing solution ouabain (100 microM) produced a 30% fall in the internal K content. 7. It is concluded that these effects of Li, and their alteration by ouabain, reflect the activity of a mechanism for the active extrusion of Li ions. It is suggested that the mechanism for the active extrusion of Li is the same as that for Na. 8. There also seems to be a site for Li that controls the phosphate efflux and which is half-maximally activated with external Li concentrations of about 2-4 mM.

Efflux of inorganic phosphate from mammalian non-myelinated nerve fibres.

1. Uptake and release of radiophosphate were measured in desheathed rabbit vagus nerve. 2. During incubation in Locke containing 0.2 mM-[32P]phosphate a slow labelling of water soluble compounds of the nerve was found; the labelling of the non water soluble compounds was much smaller. During washing with inactive Locke, the label was almost entirely released from the water soluble compounds; the radioactivity of these compounds was therefore used as the basis for the calculation of the efflux rate constants. 3. The efflux of radiophosphate increased with increasing phosphate concentration of the washing fluid. 4. A similar effect of external phosphate on the efflux of radiophosphate was seen when the phosphate concentration was suddenly changed. The rate constants were in 0.2 mM-phosphate 1.29 X 10(-3) min-1, in 0.2 mM 1.95 X 10(-3) min-1, and in 2 mM 3.21 X 10(-3) min-1 at 37 degrees C. After changing the external solution the efflux reached a new level with a time constant of about 9 min. 5. Addition of arsenate also increased the efflux of radiophosphate; on a molar basis the effect of arsenate was slightly smaller than the effect of phosphate. 6. Addition of malate or malonate did not affect the efflux of radiophosphate. 7. When the Na of the Locke was replaced by Tris, the efflux of radiophosphate was lowered by 76%, the new level was reached with a time constant of 7.7 min. In Tris-Locke changes in external phosphate did not affect the phosphate efflux. 8. A lowering of the phosphate efflux by 52% was found in Li-Locke; the efflux was then no longer affected by the external phosphate concentration. 9. The effect of external phosphate on the efflux and in the radiophosphate was also measured at intermediate Na concentrations. At different Na concentrations the ratio between the Na dependent effluxes in 2 and 0.2 mM-phosphate was approximately equal to the ratio between the Na dependent influxes in 2 and 0.2 mM-phosphate. 10. The efflux of 22Na had a rate constant of 0.050 min-1 in Locke and 0.046 min-1 in Tris-Locke. 11. It is concluded that part of the efflux of phosphate is mediated by a Na-dependent transport system; the system appears to be able to exchange phosphate between the inside and the outside and to mediate net movements of phosphate in both directions.

Adenosine promoted accumulation of adenosine 3′,5′-monophosphate in rabbit vagus nerve

Desheathed rabbit vagus nerve has been found to form cyclic AMP when incubated with adenosine. This accumulation of cyclic AMP is inhibited by theophylline but not by antiadrenergic agents, anticholinergic agents or local anaesthetics. Depolarizing media are not able to promote cyclic AMP accumulation in this preparation.

The effect of isoxsuprine on non-myelinated nerve fibres

A study has been made of the effect of isoxsuprine on non-myelinated nerve fibres of the desheathed rabbit vagus. Isoxsuprine did not affect the membrane potential, the membrane resistance, or the sodium pump activity. Isoxsuprine diminished the amplitude and rise time of the compound action potential. This indicates that isoxsuprine decreased the peak sodium current during the action potential. This local anesthetic action of isoxsuprine is more pronounced than that of lidocaine.

Uptake of orthophosphate by rabbit vagus nerve fibres.

1. The uptake of orthophosphate and its incorporation into ATP, ADP, and creatine phosphate (CrP) were studied in desheathed rabbit vagus nerve. 2. Using -32P labelled orthophosphate, the total amount of labelled phosphate taken up by the preparation was continuously recorded in a perfusion apparatus. For measuring the incorporation into phosphorylated compounds, phosphate esters and inorganic phosphate were extracted, separated and their total amount and radioactivity determined. 3. The total uptake of phosphate was found to be a biexponential function of time. 4. The time constant of the first process was 10-20 min and independent of the extracellular phosphate concentration, the final amount labelled by this process was relatively small and proportional to external phosphate, increasing from 0.026 m-mole/kg wet nerve at 0-04 mM phosphate to 1-14 m-mole/kg at 5nM. 5. The time constant of the second process depended on the extracellular phosphate concentration varying from 4624 min at 0-04 mM to 210 min at 5 mM. The final amount labelled by this process was 5-6 m-mole/kg wet wt. and independent of the extracellular phosphate. 6. The kinetics of the slow uptake were consistent with the presence of a saturable process and a non-saturable one. 7. Extraction of ATP, ADP, and the sum of CrP and Pi, showed that the total amount of these compounds remained constant for 2 hr while their radioactivity increased slowly, approximately at the same rate as the slow fraction. 8. Increasing the external phosphate from 0-04 to 5 nM increased the amount of labelled ATP. 9. A comparison with the metabolic turnover of phosphate, estimated from the oxygen consumption, shows that uptake is much slower than metabolism, so that the slow appearance of labelled nucleotides is very probably due to a limitation of the influx. 10. From the experimental data the influx can then be calculated for various phosphate concentrations. It is close to that found in squid axons.

The effect of carticain on mammalian non-myelinated nerve fibres

A study has been made of the effect of carticain, a drug structurally related to lidocaine and prilocaine, on non-myelinated nerve fibres of the desheathed rabbit vagus. Carticain did not affect the membrane potential, the membrane resistance, or the sodium pump activity. Carticain decreased the amplitude and rise time of the action potential and decreased the conduction velocity of the nerve. This indicates, that carticain diminished sodium influx during the action potential. It is concluded that carticain produces a specific local anesthetic effect in non-myelinated nerve fibres of the rabbit vagus, which is comparable to the action of lidocaine.

The effect of droperidol on mammalian non-myelinated nerve fibres

A study has been made of the effect of droperidol on non-myelinated nerve fibres of the desheathed rabbit vagus. Droperidol did not affect membrane permeability nor the sodium pump activity of the nerve fibres. A specific reduction of sodium influx during the action potential was found in the presence of the drug. Such a specific effect was also observed with local anaesthetics. The potency of droperidol with respect to this action appears to be about 10 times that of lidocaine.