Effects of Benzocaine on the Kinetics of Normal and Batrachotoxin-modified Na Channels in Frog Node of Ranvier

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 1986 Sep 1

PMID 2428413

Citations 9

Authors

M F Schneider

J M Dubois

Affiliations

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Abstract

The effects of benzocaine (0.5-1 mM) on normal Na currents, and on Na current and gating charge movement (Q) of batrachotoxin (BTX)-modified Na channels were analyzed in voltage-clamped frog node of Ranvier. Without BTX treatment the decay of Na current during pulses to between -40 and 0 mV could be decomposed into two exponential components both in the absence and in the presence of benzocaine. Benzocaine did not significantly alter the inactivation time constant of either component, but reduced both their amplitudes. The amplitude of the slow inactivating component was more decreased by benzocaine than the amplitude of the fast one, leading to an apparently faster decline of the overall Na current. After removal of Na inactivation and charge movement immobilization by BTX, benzocaine decreased the amplitude of INa with no change in time course. INa, QON, and QOFF were all reduced by the same factor. The results suggest that the rate of reaction of benzocaine with its receptor is slow compared to the rates of channel activation and inactivation. The differential effects of benzocaine on the two components of Na current inactivation in normal channels can be explained assuming two types of channel with different rates of inactivation and different affinities for the drug.

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References

Strichartz G . The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine. J Gen Physiol. 1973; 62(1):37-57. PMC: 2226105. DOI: 10.1085/jgp.62.1.37. View

Dubois J, Schneider M . Kinetics of intramembrane charge movement and conductance activation of batrachotoxin-modified sodium channels in frog node of Ranvier. J Gen Physiol. 1985; 86(3):381-94. PMC: 2228801. DOI: 10.1085/jgp.86.3.381. View

Khodorov B, Peganov E, Revenko S, Shishkova L . Sodium currents in voltage clamped nerve fiber of frog under the combined action of batrachotoxin and procaine. Brain Res. 1975; 84(3):541-6. DOI: 10.1016/0006-8993(75)90771-4. View

Hille B . Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol. 1977; 69(4):497-515. PMC: 2215053. DOI: 10.1085/jgp.69.4.497. View

Chiu S . Inactivation of sodium channels: second order kinetics in myelinated nerve. J Physiol. 1977; 273(3):573-96. PMC: 1353749. DOI: 10.1113/jphysiol.1977.sp012111. View

Nonner W, Rojas E, Stampfli R . Asymmetrical displacement currents in the membrane of frog myelinated nerve: early time course and effects of membrane potential. Pflugers Arch. 1978; 375(1):75-85. DOI: 10.1007/BF00584151. View

Khodorov B, Revenko S . Further analysis of the mechanisms of action of batrachotoxin on the membrane of myelinated nerve. Neuroscience. 1979; 4(9):1315-30. DOI: 10.1016/0306-4522(79)90159-3. View

Nonner W . Relations between the inactivation of sodium channels and the immobilization of gating charge in frog myelinated nerve. J Physiol. 1980; 299:573-603. PMC: 1279243. DOI: 10.1113/jphysiol.1980.sp013143. View

Neumcke B, Schwarz W, Stampfli R . Modification of sodium inactivation in myelinated nerve by Anemonia toxin II and iodate. Analysis of current fluctuations and current relaxations. Biochim Biophys Acta. 1980; 600(2):456-66. DOI: 10.1016/0005-2736(80)90448-4. View

10.

Schmidtmayer J, ULBRICHT W . Interaction of lidocaine and benzocaine in blocking sodium channels. Pflugers Arch. 1980; 387(1):47-54. DOI: 10.1007/BF00580843. View

11.

Sigworth F . Covariance of nonstationary sodium current fluctuations at the node of Ranvier. Biophys J. 1981; 34(1):111-33. PMC: 1327457. DOI: 10.1016/S0006-3495(81)84840-0. View

12.

Khodorov B . Sodium inactivation and drug-induced immobilization of the gating charge in nerve membrane. Prog Biophys Mol Biol. 1981; 37(2):49-89. DOI: 10.1016/0079-6107(82)90020-7. View

13.

Neumcke B, Schwarz W, Stampfli R . Block of Na channels in the membrane of myelinated nerve by benzocaine. Pflugers Arch. 1981; 390(3):230-6. DOI: 10.1007/BF00658267. View

14.

Cahalan M, Almers W . Interactions between quaternary lidocaine, the sodium channel gates, and tetrodotoxin. Biophys J. 1979; 27(1):39-55. PMC: 1328546. DOI: 10.1016/S0006-3495(79)85201-7. View

15.

Ochs G, Bromm B, Schwarz J . A three-state model for inactivation of sodium permeability. Biochim Biophys Acta. 1981; 645(2):243-52. DOI: 10.1016/0005-2736(81)90195-4. View

16.

Dubois J, Schneider M . Kinetics of intramembrane charge movement and sodium current in frog node of Ranvier. J Gen Physiol. 1982; 79(4):571-602. PMC: 2215479. DOI: 10.1085/jgp.79.4.571. View

17.

Neumcke B, Stampfli R . Sodium currents and sodium-current fluctuations in rat myelinated nerve fibres. J Physiol. 1982; 329:163-84. PMC: 1224773. DOI: 10.1113/jphysiol.1982.sp014296. View

18.

Dubois J, Khodorov B . Batrachotoxin protects sodium channels from the blocking action of oenanthotoxin. Pflugers Arch. 1982; 395(1):55-8. DOI: 10.1007/BF00584968. View

19.

Dubois J, Schneider M, Khodorov B . Voltage dependence of intramembrane charge movement and conductance activation of batrachotoxin-modified sodium channels in frog node of Ranvier. J Gen Physiol. 1983; 81(6):829-44. PMC: 2215561. DOI: 10.1085/jgp.81.6.829. View

20.

Benoit E, CORBIER A, Dubois J . Evidence for two transient sodium currents in the frog node of Ranvier. J Physiol. 1985; 361:339-60. PMC: 1192863. DOI: 10.1113/jphysiol.1985.sp015649. View