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. 1993 Aug;109(4):1239–1246. doi: 10.1111/j.1476-5381.1993.tb13755.x

Differential inhibition of a transient K+ current by chlorpromazine and 4-aminopyridine in neurones of the rat dorsal root ganglia.

N Ogata 1, H Tatebayashi 1
PMCID: PMC2175770  PMID: 8401935

Abstract

1. K+ currents were recorded from neurones of the newborn rat cultured dorsal root ganglia, by a whole cell variation of the patch-clamp technique. 2. Chlorpromazine (CPZ), a neuroleptic, reversibly reduced the amplitude of the transient K+ current (referred to as 'IT' hereafter) with a dissociation constant (Kd) of 4.5 microM. The inhibition of the delayed rectifier K+ current (IDR) was much less potent (Kd, 120 microM). CPZ (100 microM) had no effect on the inward rectifier K+ current. 3. The blocking action of CPZ on IT was about seven times more potent than that of 4-aminopyridine (4-AP) which had a Kd of 31 microM. The inhibition of IT followed one-to-one binding stoichiometry with both drugs. 4. The decay time course of IT was not affected by CPZ, whereas 4-AP markedly accelerated the decay phase of IT. 5. The steady-state inactivation curve of IT was shifted in the negative direction (about 5 mV) by CPZ, whereas the curve was shifted in the positive direction (about 13 mV) by 4-AP. 6. The recovery from inactivation as measured by a conventional double pulse protocol was described by two exponential components in the control solution. CPZ markedly reduced the first component and slowed down the recovery from inactivation. In contrast, in the presence of 4-AP, the peak amplitude of IT was rather increased by a preceding IT possibly through voltage-dependent unbinding of 4-AP molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Alger B. E., Nicoll R. A. Epileptiform burst afterhyperolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science. 1980 Dec 5;210(4474):1122–1124. doi: 10.1126/science.7444438. [DOI] [PubMed] [Google Scholar]
  2. Coraboeuf E., Carmeliet E. Existence of two transient outward currents in sheep cardiac Purkinje fibers. Pflugers Arch. 1982 Feb;392(4):352–359. doi: 10.1007/BF00581631. [DOI] [PubMed] [Google Scholar]
  3. Dinan T. G., Crunelli V., Kelly J. S. Neuroleptics decrease calcium-activated potassium conductance in hippocampal pyramidal cells. Brain Res. 1987 Mar 24;407(1):159–162. doi: 10.1016/0006-8993(87)91231-5. [DOI] [PubMed] [Google Scholar]
  4. Escande D., Coulombe A., Faivre J. F., Deroubaix E., Coraboeuf E. Two types of transient outward currents in adult human atrial cells. Am J Physiol. 1987 Jan;252(1 Pt 2):H142–H148. doi: 10.1152/ajpheart.1987.252.1.H142. [DOI] [PubMed] [Google Scholar]
  5. Gustafsson B., Galvan M., Grafe P., Wigström H. A transient outward current in a mammalian central neurone blocked by 4-aminopyridine. Nature. 1982 Sep 16;299(5880):252–254. doi: 10.1038/299252a0. [DOI] [PubMed] [Google Scholar]
  6. HUANG C. L., RUSKIN B. H. DETERMINATION OF SERUM CHLORPROMAZINE METABOLITES IN PSYCHOTIC PATIENTS. J Nerv Ment Dis. 1964 Oct;139:381–386. doi: 10.1097/00005053-196410000-00011. [DOI] [PubMed] [Google Scholar]
  7. Hagiwara S., Yoshii M. Effects of internal potassium and sodium on the anomalous rectification of the starfish egg as examined by internal perfusion. J Physiol. 1979 Jul;292:251–265. doi: 10.1113/jphysiol.1979.sp012849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  9. Hidaka H., Sasaki Y., Tanaka T., Endo T., Ohno S., Fujii Y., Nagata T. N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, inhibits cell proliferation. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4354–4357. doi: 10.1073/pnas.78.7.4354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hille B. Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol. 1977 Apr;69(4):497–515. doi: 10.1085/jgp.69.4.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hondeghem L. M., Katzung B. G. Time- and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium channels. Biochim Biophys Acta. 1977 Nov 14;472(3-4):373–398. doi: 10.1016/0304-4157(77)90003-x. [DOI] [PubMed] [Google Scholar]
  12. McCann J. D., Welsh M. J. Neuroleptics antagonize a calcium-activated potassium channel in airway smooth muscle. J Gen Physiol. 1987 Feb;89(2):339–352. doi: 10.1085/jgp.89.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ogata N., Narahashi T. Block of sodium channels by psychotropic drugs in single guinea-pig cardiac myocytes. Br J Pharmacol. 1989 Jul;97(3):905–913. doi: 10.1111/j.1476-5381.1989.tb12031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ogata N., Narahashi T. Potent blocking action of chlorpromazine on two types of calcium channels in cultured neuroblastoma cells. J Pharmacol Exp Ther. 1990 Mar;252(3):1142–1149. [PubMed] [Google Scholar]
  15. Ogata N., Nishimura M., Narahashi T. Kinetics of chlorpromazine block of sodium channels in single guinea pig cardiac myocytes. J Pharmacol Exp Ther. 1989 Feb;248(2):605–613. [PubMed] [Google Scholar]
  16. Ogata N., Tatebayashi H. A simple and multi-purpose "concentration-clamp" method for rapid superfusion. J Neurosci Methods. 1991 Sep;39(2):175–183. doi: 10.1016/0165-0270(91)90083-c. [DOI] [PubMed] [Google Scholar]
  17. Ogata N., Tatebayashi H. Comparison of two types of Na+ currents with low-voltage-activated T-type Ca2+ current in newborn rat dorsal root ganglia. Pflugers Arch. 1992 Apr;420(5-6):590–594. doi: 10.1007/BF00374638. [DOI] [PubMed] [Google Scholar]
  18. Ogata N., Tatebayashi H. Modulation of sodium current kinetics by chlorpromazine in freshly-isolated striatal neurones of the adult guinea-pig. Br J Pharmacol. 1989 Dec;98(4):1173–1184. doi: 10.1111/j.1476-5381.1989.tb12662.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ogata N., Yoshii M., Narahashi T. Differential block of sodium and calcium channels by chlorpromazine in mouse neuroblastoma cells. J Physiol. 1990 Jan;420:165–183. doi: 10.1113/jphysiol.1990.sp017906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Risch S. C., Groom G. P., Janowsky D. S. Interfaces of psychopharmacology and cardiology--part one. J Clin Psychiatry. 1981 Jan;42(1):23–34. [PubMed] [Google Scholar]
  21. Robbins J., Sim J. A. A transient outward current in NG108-15 neuroblastoma x glioma hybrid cells. Pflugers Arch. 1990 Apr;416(1-2):130–137. doi: 10.1007/BF00370234. [DOI] [PubMed] [Google Scholar]
  22. Ruppersberg J. P., Frank R., Pongs O., Stocker M. Cloned neuronal IK(A) channels reopen during recovery from inactivation. Nature. 1991 Oct 17;353(6345):657–660. doi: 10.1038/353657a0. [DOI] [PubMed] [Google Scholar]
  23. Seeman P. Brain dopamine receptors. Pharmacol Rev. 1980 Sep;32(3):229–313. [PubMed] [Google Scholar]
  24. Simurda J., Simurdová M., Christé G. Use-dependent effects of 4-aminopyridine on transient outward current in dog ventricular muscle. Pflugers Arch. 1989 Nov;415(2):244–246. doi: 10.1007/BF00370600. [DOI] [PubMed] [Google Scholar]
  25. Stansfeld C. E., Marsh S. J., Halliwell J. V., Brown D. A. 4-Aminopyridine and dendrotoxin induce repetitive firing in rat visceral sensory neurones by blocking a slowly inactivating outward current. Neurosci Lett. 1986 Mar 14;64(3):299–304. doi: 10.1016/0304-3940(86)90345-9. [DOI] [PubMed] [Google Scholar]
  26. Storm J. F. Temporal integration by a slowly inactivating K+ current in hippocampal neurons. Nature. 1988 Nov 24;336(6197):379–381. doi: 10.1038/336379a0. [DOI] [PubMed] [Google Scholar]
  27. Tatebayashi H., Ogata N. Kinetic analysis of the GABAB-mediated inhibition of the high-threshold Ca2+ current in cultured rat sensory neurones. J Physiol. 1992 Feb;447:391–407. doi: 10.1113/jphysiol.1992.sp019008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Thompson S. Aminopyridine block of transient potassium current. J Gen Physiol. 1982 Jul;80(1):1–18. doi: 10.1085/jgp.80.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]

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