The Kinetics of Local Anesthetic Blockade of End-plate Channels

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 1982 Mar 1

PMID 6978739

Citations 17

Authors

R L Ruff

Affiliations

Soon will be listed here.

Abstract

The effect of the local anesthetic QX222 on the kinetics of miniature end-plate currents (MEPC)and acetylcholine-induced end-plate current fluctuations was studied in voltage-clamped frog cutaneous pectoris neuromuscular junctions. The rate constants for a kinetic scheme of local anesthetic blockage of end-plate channels were calculated from the MEPC decay parameters. At 18 degrees C the blocking rate constant was 1.1 +/- 0.3 x 10(7) exp (-0.009 +/- 0.003 x V)s -1M-1, and the unblocking rate constant was 5.7 +/- 0.6 exp (0.011 +/- 0.002 x V)s -1. The dissociation constant was close to 10 microM at -80 mV. End-plate fluctuations indicated that the local anesthetic QX222 lowered the effective single-channel conductance, suggesting a finite blocked state conductance that was calculated to be 1.6 pS. The apparent differences between QX222 interaction with end-plate and extrajunctional channels are discussed.

Citing Articles

Effect of 50% enantiomeric excess bupivacaine mixture combined with pancuronium on neuromuscular transmission in rat phrenic nerve-diaphragm preparation; a pilot study.

Braga A, Carvalho V, Braga F, Poterio G, Santos F, Junqueira F Indian J Anaesth. 2016; 59(11):701-5.

PMID: 26755834 PMC: 4697241. DOI: 10.4103/0019-5049.170019.

Altered neurotransmitter release machinery in mice deficient for the deubiquitinating enzyme Usp14.

Bhattacharyya B, Wilson S, Jung H, Miller R Am J Physiol Cell Physiol. 2011; 302(4):C698-708.

PMID: 22075695 PMC: 3287356. DOI: 10.1152/ajpcell.00326.2010.

Neuromuscular blocking profile of the vecuronium analogue, Org-9487, in the rat isolated hemidiaphragm preparation.

Prior C, Tian L, el Mallah A, Young L, Ward J Br J Pharmacol. 1995; 116(7):3049-55.

PMID: 8680742 PMC: 1909232. DOI: 10.1111/j.1476-5381.1995.tb15962.x.

Local anaesthetic blockade of neuronal nicotinic ACh receptor-channels in rat parasympathetic ganglion cells.

Cuevas J, Adams D Br J Pharmacol. 1994; 111(3):663-72.

PMID: 7517326 PMC: 1910063. DOI: 10.1111/j.1476-5381.1994.tb14789.x.

Preventing errors when estimating single channel properties from the analysis of current fluctuations.

Silberberg S, Magleby K Biophys J. 1993; 65(4):1570-84.

PMID: 7506065 PMC: 1225883. DOI: 10.1016/S0006-3495(93)81196-2.

References

Gage P, ARMSTRONG C . Miniature end-plate currents in voltage-clamped muscle fibre. Nature. 1968; 218(5139):363-5. DOI: 10.1038/218363b0. View

Steinbach A . Alteration by xylocaine (lidocaine) and its derivatives of the time course of the end plate potential. J Gen Physiol. 1968; 52(1):144-61. PMC: 2225792. DOI: 10.1085/jgp.52.1.144. View

Steinbach A . A kinetic model for the action of xylocaine on receptors for acetylcholine. J Gen Physiol. 1968; 52(1):162-80. PMC: 2225784. DOI: 10.1085/jgp.52.1.162. View

Maeno T, Edwards C, HASHIMURA S . Difference in effects of end-plate potentials between procaine and lidocaine as revealed by voltage-clamp experiments. J Neurophysiol. 1971; 34(1):32-46. DOI: 10.1152/jn.1971.34.1.32. View

Kordas M . The effect of procaine on neuromuscular transmission. J Physiol. 1970; 209(3):689-99. PMC: 1395555. DOI: 10.1113/jphysiol.1970.sp009186. View

Deguchi T, Narahashi T . Effects of procaine on ionic conductances of end-plate membranes. J Pharmacol Exp Ther. 1971; 176(2):423-33. View

Magleby K, Stevens C . The effect of voltage on the time course of end-plate currents. J Physiol. 1972; 223(1):151-71. PMC: 1331438. DOI: 10.1113/jphysiol.1972.sp009839. View

Magleby K, Stevens C . A quantitative description of end-plate currents. J Physiol. 1972; 223(1):173-97. PMC: 1331439. DOI: 10.1113/jphysiol.1972.sp009840. View

Kordas M . An attempt at an analysis of the factors determining the time course of the end-plate current. I. The effects of prostigmine and of the ratio of Mg 2+ to Ca 2+ . J Physiol. 1972; 224(2):317-32. PMC: 1331492. DOI: 10.1113/jphysiol.1972.sp009897. View

10.

Kordas M . An attempt at an analysis of the factors determining the time course of the end-plate current. II. Temperature. J Physiol. 1972; 224(2):333-48. PMC: 1331493. DOI: 10.1113/jphysiol.1972.sp009898. View

11.

Gage P, McBurney R . Miniature end-plate currents and potentials generated by quanta of acetylcholine in glycerol-treated toad sartorius fibres. J Physiol. 1972; 226(1):79-94. PMC: 1331154. DOI: 10.1113/jphysiol.1972.sp009974. View

12.

Woodhull A . Ionic blockage of sodium channels in nerve. J Gen Physiol. 1973; 61(6):687-708. PMC: 2203489. DOI: 10.1085/jgp.61.6.687. View

13.

Anderson C, Stevens C . Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction. J Physiol. 1973; 235(3):655-91. PMC: 1350786. DOI: 10.1113/jphysiol.1973.sp010410. View

14.

Colquhoun D, Dionne V, Steinbach J, Stevens C . Conductance of channels opened by acetylcholine-like drugs in muscle end-plate. Nature. 1975; 253(5488):204-6. DOI: 10.1038/253204a0. View

15.

Magleby K, Terrar D . Factors affecting the time course of decay of end-plate currents: a possible cooperative action of acetylcholine on receptors at the frog neuromuscular junction. J Physiol. 1975; 244(2):467-95. PMC: 1330772. DOI: 10.1113/jphysiol.1975.sp010808. View

16.

Katz B, Miledi R . The effect of procaine on the action of acetylcholine at the neuromuscular junction. J Physiol. 1975; 249(2):269-84. PMC: 1309574. DOI: 10.1113/jphysiol.1975.sp011015. View

17.

Dionne V, Stevens C . Voltage dependence of agonist effectiveness at the frog neuromuscular junction: resolution of a paradox. J Physiol. 1975; 251(2):245-70. PMC: 1348425. DOI: 10.1113/jphysiol.1975.sp011090. View

18.

Neher E, Sakmann B . Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature. 1976; 260(5554):799-802. DOI: 10.1038/260799a0. View

19.

Ruff R . Local anesthetic alteration of miniature endplate currents and endplate current fluctuations. Biophys J. 1976; 16(5):433-9. PMC: 1334865. DOI: 10.1016/S0006-3495(76)85699-8. View

20.

Beam K . A voltage-clamp study of the effect of two lidocaine derivatives on the time course of end-plate currents. J Physiol. 1976; 258(2):279-300. PMC: 1308976. DOI: 10.1113/jphysiol.1976.sp011420. View