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. 1980 Jan;68(1):99–106. doi: 10.1111/j.1476-5381.1980.tb10704.x

Actions of 4-aminopyridine on vascular smooth muscle tissues of the guinea-pig

Yusuke Hara, Kenji Kitamura, Hirosi Kuriyama
PMCID: PMC2044094  PMID: 7357204

Abstract

1 Effects of 4-aminopyridine (4-AP) and procaine on the membrane and contractile properties of smooth muscle cells of the guinea-pig pulmonary artery and portal vein were observed.

2 The membrane potential and length constant of smooth muscle cells of the guinea-pig pulmonary artery were -53.2 mV and 1.2 mm, respectively, and those of the portal vein were -52.6 mV and 0.71 mm, respectively. The membrane was electrically quiescent in the pulmonary artery and it was electrically active in the portal vein.

3 Both 4-AP and procaine depolarized the membrane, increased the membrane resistance and suppressed the rectifying properties in both tissues. Both agents evoked a graded response from the muscle membranes of the pulmonary artery by outward current pulse. Procaine had a greater effect than 4-AP on the above membrane properties.

4 4-AP (10-5 M) produced contraction without depolarization of the membrane. The contraction evoked by 10-5 M 4-AP was completely suppressed but that evoked by 5 × 10-4 M 4-AP was only partly suppressed by phentolamine (10-7 M). However, the contraction evoked by procaine was not suppressed by phentolamine.

5 4-AP enhanced but procaine suppressed the amplitude of 118 mM [K]0-induced contraction.

6 The results suggest that 4-AP and procaine suppress K-conductance of the muscle membrane, and 4-AP but not procaine increases noradrenaline release from the nerve terminal. Presumably intracellular free Ca concentrations are also modified by these agents. The effects of 4-AP and procaine on the vascular muscle were compared with those on other excitable tissues.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abe Y., Tomita T. Cable properties of smooth muscle. J Physiol. 1968 May;196(1):87–100. doi: 10.1113/jphysiol.1968.sp008496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BULBRING E. Membrane potentials of smooth muscle fibres of the taenia coli of the guinea-pig. J Physiol. 1954 Aug 27;125(2):302–315. doi: 10.1113/jphysiol.1954.sp005159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Casteels R., Kitamura K., Kuriyama H., Suzuki H. Excitation-contraction coupling in the smooth muscle cells of the rabbit main pulmonary artery. J Physiol. 1977 Sep;271(1):63–79. doi: 10.1113/jphysiol.1977.sp011990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Casteels R., Kitamura K., Kuriyama H., Suzuki H. The membrane properties of the smooth muscle cells of the rabbit main pulmonary artery. J Physiol. 1977 Sep;271(1):41–61. doi: 10.1113/jphysiol.1977.sp011989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Gillespie J. S., Tilmisany A. K. The action of tetraethyl-ammonium chloride on the response of the rat anococcygeus muscle to motor and inhibitory nerve stimulation and to some drugs. Br J Pharmacol. 1976 Sep;58(1):47–55. doi: 10.1111/j.1476-5381.1976.tb07692.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Haeusler G. Relationship between noradrenaline-induced depolarization and contraction in vascular smooth muscle. Blood Vessels. 1978;15(1-3):46–54. doi: 10.1159/000158152. [DOI] [PubMed] [Google Scholar]
  9. Ito Y., Kuriyama H., Sakamoto Y. Effects of tetraethylammonium chloride on the membrane activity of guinea-pig stomach smooth muscle. J Physiol. 1970 Dec;211(2):445–460. doi: 10.1113/jphysiol.1970.sp009286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ito Y., Suzuki H., Kuriyama H. On the roles of calcium ion during potassium induced contracture in the smooth muscle cells of the rabbit main pulmonary artery. Jpn J Physiol. 1977;27(6):755–770. doi: 10.2170/jjphysiol.27.755. [DOI] [PubMed] [Google Scholar]
  11. KOKETSU K. Action of tetraethylammonium chloride on neuromuscular transmission in frogs. Am J Physiol. 1958 Apr;193(1):213–218. doi: 10.1152/ajplegacy.1958.193.1.213. [DOI] [PubMed] [Google Scholar]
  12. Katz B., Miledi R. Spontaneous and evoked activity of motor nerve endings in calcium Ringer. J Physiol. 1969 Aug;203(3):689–706. doi: 10.1113/jphysiol.1969.sp008887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Keatinge W. R. Mechanism of slow discharges of sheep carotid artery. J Physiol. 1978 Jun;279:275–289. doi: 10.1113/jphysiol.1978.sp012344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kirpekar M., Kirpekar S. M., Prat J. C. Effect of 4-aminopyridine on release of noradrenaline from the perfused cat spleen by nerve stimulation. J Physiol. 1977 Nov;272(3):517–528. doi: 10.1113/jphysiol.1977.sp012057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kirpekar S. M., Wakade A. R., Prat J. C. Effect of tetraethylammonium and barium on the release of noradrenaline from the perfused cat spleen by nerve stimulation and potassium. Naunyn Schmiedebergs Arch Pharmacol. 1976 Jul;294(1):23–29. doi: 10.1007/BF00692781. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Kurihara S. The effect of procaine on the mechanical and electrical activities of the smooth muscle cells of the guineal pig urinary bladder. Jpn J Physiol. 1975;25(6):775–788. doi: 10.2170/jjphysiol.25.775. [DOI] [PubMed] [Google Scholar]
  18. Kuriyama H., Oshima K., Sakamoto Y. The membrane properties of the smooth muscle of the guinea-pig portal vein in isotonic and hypertonic solutions. J Physiol. 1971 Aug;217(1):179–199. doi: 10.1113/jphysiol.1971.sp009565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kuriyama H., Suzuki H. Electrical property and chemical sensitivity of vascular smooth muscles in normotensive and spontaneously hypersensitive rats. J Physiol. 1978 Dec;285:409–424. doi: 10.1113/jphysiol.1978.sp012579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Llinás R., Walton K., Bohr V. Synaptic transmission in squid giant synapse after potassium conductance blockage with external 3- and 4-aminopyridine. Biophys J. 1976 Jan;16(1):83–86. doi: 10.1016/S0006-3495(76)85664-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lundh H., Leander S., Thesleff S. Antagonism of the paralysis produced by botulinum toxin in the rat. The effects of tetraethylammonium, guanidine and 4-aminopyridine. J Neurol Sci. 1977 May;32(1):29–43. doi: 10.1016/0022-510x(77)90037-5. [DOI] [PubMed] [Google Scholar]
  22. Lundh H., Thesleff S. The mode of action of 4-aminopyridine and guanidine on transmitter release from motor nerve terminals. Eur J Pharmacol. 1977 Apr 21;42(4):411–412. doi: 10.1016/0014-2999(77)90176-5. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Narahashi T., Frazier D. T., Takeno K. Effects of calcium on the local anesthetic suppression of ionic conductances in squid axon membranes. J Pharmacol Exp Ther. 1976 May;197(2):426–438. [PubMed] [Google Scholar]
  25. Narahashi T., Frazier T., Yamada M. The site of action and active form of local anesthetics. I. Theory and pH experiments with tertiary compounds. J Pharmacol Exp Ther. 1970 Jan;171(1):32–44. [PubMed] [Google Scholar]
  26. Osa T., Kuriyama H. The membrane properties and decremental conduction of excitation in the fundus of the guinea-pig stomach. Jpn J Physiol. 1970 Dec 15;20(6):626–639. doi: 10.2170/jjphysiol.20.626. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Thoenen H., Haefely W., Staehelin H. Potentiation by tetraethylammonium of the response of the cat spleen to postganglionic sympathetic nerve stimulation. J Pharmacol Exp Ther. 1967 Sep;157(3):532–540. [PubMed] [Google Scholar]
  29. Yeh J. Z., Oxford G. S., Wu C. H., Narahashi T. Interactions of aminopyridines with potassium channels of squid axon membranes. Biophys J. 1976 Jan;16(1):77–81. doi: 10.1016/S0006-3495(76)85663-9. [DOI] [PMC free article] [PubMed] [Google Scholar]

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