Abstract
1. Voltage-clamped end-plate currents (e.p.c.s) have been studied in the glycerol-treated Rana pipiens sartorius nerve-muscle preparations in normal Ringer solution and in the presence of QX-222 and QX-314. 2. Both QX-222 and QX-314, the trimethyl and triethyl analogues, respectively, of lidocaine, greatly modify end-plate current kinetics. The altered e.p.c.s still show a true reversal potential, which is essentially the same as the reversal potential before drug treatment. The time course of the altered end-plate currents varies with both membrane potential and drug concentration. 3. In the presence of 0-1-1-0 mM QX-222, end-plate currents decay as the sum of three exponentials: I(t) =I1(0)e-k1t+I2(0)e-k2t+I3(0)e-k3t, where the subscipts 1, 2 and 3 refer to the rapidly, intermediately, and slowly decaying components, respectively. Both the amplitudes, Ij(0), and the decay rates, kj, depend upon membrane potential. 4. Hyperpolarization increases the relative size of the first and third components, i.e. I1(0) and I3(0) increase relative to I2(0). Depolarization increases the relative size of the second component. 5. Hyperpolarization causes a decrease in the decay rates k2 and k3 and causes a slight increase in the decay rate k1. Dependence of the three decay rates on membrane potential is well described by: kj=bjeajv. 6. The Q10 of each of the kj is about 3. 7. Raising QX-222 concentration, at any given membrane potential, augments I1(0) and I3(0) at the expense of I2(0). Raising concentration increases k1 and decreases k3; their voltage-dependence is little affected. 8. At all QX-222 concentrations tested the decay rate k2 is nearly the same as the decay rate of a normal e.p.c. recorded at an equivalent holding potential from the same fibre before drug exposure. 9. End-plate currents in the presence of 0-1 mM-QX-314 show a "major" or rapidly decaying phase and a very small, slowly decaying phase or "tail", but no intermediate component. Only the major component is discernible for end-plate currents in 0-5 mM-QX-314. 10. Voltage- and concentration-dependence of the decay rate of the major component in QX-314 is similar to k1 and QX-222. Voltage-dependence of the tails decay rate appears to be similar to k3. It is hypothesized that the second component in QX-222 represents currents of unaltered or normal conductance kinetics, and that the first and third components in QX-222, as well as the major component and tail in QX-314, represent current of "QX-altered conductance kinetics".
Full text
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson C. R., Stevens C. F. Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction. J Physiol. 1973 Dec;235(3):655–691. doi: 10.1113/jphysiol.1973.sp010410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beam K. G. A quantitative description of end-plate currents in the presence of two lidocaine derivatives. J Physiol. 1976 Jun;258(2):301–322. doi: 10.1113/jphysiol.1976.sp011421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beránek R., Vyskocil F. The effect of atropine on the frog sartorius neuromuscular junction. J Physiol. 1968 Mar;195(2):493–503. doi: 10.1113/jphysiol.1968.sp008470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Connor J. A., Stevens C. F. Inward and delayed outward membrane currents in isolated neural somata under voltage clamp. J Physiol. 1971 Feb;213(1):1–19. doi: 10.1113/jphysiol.1971.sp009364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Deguchi T., Narahashi T. Effects of procaine on ionic conductances of end-plate membranes. J Pharmacol Exp Ther. 1971 Feb;176(2):423–433. [PubMed] [Google Scholar]
- FALK G., FATT P. LINEAR ELECTRICAL PROPERTIES OF STRIATED MUSCLE FIBRES OBSERVED WITH INTRACELLULAR ELECTRODES. Proc R Soc Lond B Biol Sci. 1964 Apr 14;160:69–123. doi: 10.1098/rspb.1964.0030. [DOI] [PubMed] [Google Scholar]
- Gage P. W., Armstrong C. M. Miniature end-plate currents in voltage-clamped muscle fibre. Nature. 1968 Apr 27;218(5139):363–365. doi: 10.1038/218363b0. [DOI] [PubMed] [Google Scholar]
- Gage P. W., McBurney R. N. Effects of membrane potential, temperature and neostigmine on the conductance change caused by a quantum or acetylcholine at the toad neuromuscular junction. J Physiol. 1975 Jan;244(2):385–407. doi: 10.1113/jphysiol.1975.sp010805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gage P. W., McBurney R. N. Miniature end-plate currents and potentials generated by quanta of acetylcholine in glycerol-treated toad sartorius fibres. J Physiol. 1972 Oct;226(1):79–94. doi: 10.1113/jphysiol.1972.sp009974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz B., Miledi R. The effect of procaine on the action of acetylcholine at the neuromuscular junction. J Physiol. 1975 Jul;249(2):269–284. doi: 10.1113/jphysiol.1975.sp011015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kordas M. The effect of procaine on neuromuscular transmission. J Physiol. 1970 Aug;209(3):689–699. doi: 10.1113/jphysiol.1970.sp009186. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuba K., Albuquerque E. X., Daly J., Barnard E. A. A study of the irreversible cholinesterase inhibitor, diisopropylfluorophosphate, on time course of end-plate currents in frog sartorius muscle. J Pharmacol Exp Ther. 1974 May;189(2):499–512. [PubMed] [Google Scholar]
- Maeno T. Analysis of sodium and potassium conductances in the procaine end-plate potential. J Physiol. 1966 Apr;183(3):592–606. doi: 10.1113/jphysiol.1966.sp007886. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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 Jan;34(1):32–46. doi: 10.1152/jn.1971.34.1.32. [DOI] [PubMed] [Google Scholar]
- Magleby K. L., Stevens C. F. A quantitative description of end-plate currents. J Physiol. 1972 May;223(1):173–197. doi: 10.1113/jphysiol.1972.sp009840. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Magleby K. L., Stevens C. F. The effect of voltage on the time course of end-plate currents. J Physiol. 1972 May;223(1):151–171. doi: 10.1113/jphysiol.1972.sp009839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Magleby K. L., Terrar D. A. 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 Jan;244(2):467–495. doi: 10.1113/jphysiol.1975.sp010808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steinbach A. B. A kinetic model for the action of xylocaine on receptors for acetylcholine. J Gen Physiol. 1968 Jul;52(1):162–180. doi: 10.1085/jgp.52.1.162. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steinbach A. B. Alteration by xylocaine (lidocaine) and its derivatives of the time course of the end plate potential. J Gen Physiol. 1968 Jul;52(1):144–161. doi: 10.1085/jgp.52.1.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strichartz G. R. The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine. J Gen Physiol. 1973 Jul;62(1):37–57. doi: 10.1085/jgp.62.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]