Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1974 Feb;237(1):157–182. doi: 10.1113/jphysiol.1974.sp010475

The effect of contractile activity on fibrillation and extrajunctional acetylcholine-sensitivity in rat muscle maintained in organ culture

D Purves, B Sakmann
PMCID: PMC1350874  PMID: 4856656

Abstract

1. The effect of contractile activity on the initiation of spontaneous action potentials (fibrillation) and on extrajunctional acetylcholine-sensitivity has been studied in single fibres in strips of previously denervated rat diaphragm maintained in organ culture for up to 10 days.

2. Following removal of the diaphragm from the animal, fibrillation slowed and usually stopped altogether for about 24-36 hr. Thereafter, spontaneously active fibres were found in all cultured muscle strips.

3. At any one time, about ¼ to ⅓ of fibres impaled with micro-electrodes were active (defined as more than one action potential/10 sec), with a mean discharge frequency of 4·5/sec (range 0·1-24/sec).

4. The duration of continuous activity in single fibres was, on average, 21-22 hr; a period of activity was followed by a longer inactive interval. Thus activity in single fibres is cyclical.

5. Direct stimulation of fibrillating strips for 24 hr at 10/sec suppressed spontaneous activity for 1-3 days.

6. Conversely, blockade of spontaneous activity with tetrodotoxin for 72 hr led to a two- to threefold increase in the number of fibrillating fibres when the drug was washed out; in some strips nearly all fibres became spontaneously active.

7. The mean rate of activity of diaphragm fibres during normal breathing, determined by recording single units from the phrenic nerve in lightly anaesthetized animals, is about 18/sec.

8. Direct stimulation of cultured diaphragm strips in a pattern similar to breathing for 7-8 days at an average rate of 10-12/sec (or 5/sec in some experiments), resulted in a marked reduction (about 95% in experiments at 10/sec) in extrajunctional sensitivity to ionophoretically applied ACh.

9. Direct stimulation for 24 hr at 10/sec (comparable to a period of spontaneous activity) caused only a small reduction in extrajunctional ACh-sensitivity.

10. We conclude that spontaneous activity in single fibres under these conditions occurs cyclically because activity, over a period of hours, inhibits the ability of the fibrillating fibre to initiate further action potentials. Repeated self-inhibition of spontaneous activity probably explains why denervated muscle fibres remain highly sensitive to extrajunctionally applied ACh.

Full text

PDF
157

Selected References

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

  1. AXELSSON J., THESLEFF S. A study of supersensitivity in denervated mammalian skeletal muscle. J Physiol. 1959 Jun 23;147(1):178–193. doi: 10.1113/jphysiol.1959.sp006233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adrian E. D., Bronk D. W. The discharge of impulses in motor nerve fibres: Part I. Impulses in single fibres of the phrenic nerve. J Physiol. 1928 Sep 18;66(1):81–101. doi: 10.1113/jphysiol.1928.sp002509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Albuquerque E. X., McIsaac R. J. Fast and slow mammalian muscles after denervation. Exp Neurol. 1970 Jan;26(1):183–202. doi: 10.1016/0014-4886(70)90099-3. [DOI] [PubMed] [Google Scholar]
  4. Albuquerque E. X., Warnick J. E., Tasse J. R., Sansone F. M. Effects of vinblastine and colchicine on neural regulation of the fast and slow skeletal muscles of the rat. Exp Neurol. 1972 Dec;37(3):607–634. doi: 10.1016/0014-4886(72)90103-3. [DOI] [PubMed] [Google Scholar]
  5. Belmar J., Eyzaguirre C. Pacemaker site of fibrillation potentials in denervated mammmalian muscle. J Neurophysiol. 1966 May;29(3):425–441. doi: 10.1152/jn.1966.29.3.425. [DOI] [PubMed] [Google Scholar]
  6. Close R. I. Dynamic properties of mammalian skeletal muscles. Physiol Rev. 1972 Jan;52(1):129–197. doi: 10.1152/physrev.1972.52.1.129. [DOI] [PubMed] [Google Scholar]
  7. DEL CASTILLO J., KATZ B. On the localization of acetylcholine receptors. J Physiol. 1955 Apr 28;128(1):157–181. doi: 10.1113/jphysiol.1955.sp005297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drachman D. B., Witzke F. Trophic regulation of acetylcholine sensitivity of muscle: effect of electrical stimulation. Science. 1972 May 5;176(4034):514–516. doi: 10.1126/science.176.4034.514. [DOI] [PubMed] [Google Scholar]
  9. Duchen L. W., Stefani E. Electrophysiological studies of neuromuscular transmission in hereditary 'motor end-plate disease' of the mouse. J Physiol. 1971 Jan;212(2):535–548. doi: 10.1113/jphysiol.1971.sp009340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fambrough D. M. Acetylcholine sensitivity of muscle fiber membranes: mechanism of regulation by motoneurons. Science. 1970 Apr 17;168(3929):372–373. doi: 10.1126/science.168.3929.372. [DOI] [PubMed] [Google Scholar]
  11. Fischbach G. D., Robbins N. Effect of chronic disuse of rat soleus neuromuscular junctions on postsynaptic membrane. J Neurophysiol. 1971 Jul;34(4):562–569. doi: 10.1152/jn.1971.34.4.562. [DOI] [PubMed] [Google Scholar]
  12. Guth L. "Trophic" influences of nerve on muscle. Physiol Rev. 1968 Oct;48(4):645–687. doi: 10.1152/physrev.1968.48.4.645. [DOI] [PubMed] [Google Scholar]
  13. Hofmann W. W., Thesleff S. Studies on the trophic influence of nerve on skeletal muscle. Eur J Pharmacol. 1972 Dec;20(3):256–260. doi: 10.1016/0014-2999(72)90182-3. [DOI] [PubMed] [Google Scholar]
  14. Jones R., Vrbová G. Can denervation hypersensitivity be prevented? J Physiol. 1971;217 (Suppl):67P–68P. [PubMed] [Google Scholar]
  15. Jones R., Vrbová G. Effect of muscle activity on denervation hypersensitivity. J Physiol. 1970 Sep;210(2):144P–145P. [PubMed] [Google Scholar]
  16. KRNJEVIC K., MILEDI R. Failure of neuromuscular propagation in rats. J Physiol. 1958 Mar 11;140(3):440–461. [PMC free article] [PubMed] [Google Scholar]
  17. Kuffler S. W., Dennis M. J., Harris A. J. The development of chemosensitivity in extrasynaptic areas of the neuronal surface after denervation of parasympathetic ganglion cells in the heart of the frog. Proc R Soc Lond B Biol Sci. 1971 Apr 27;177(1049):555–563. doi: 10.1098/rspb.1971.0047. [DOI] [PubMed] [Google Scholar]
  18. LI C. L., ENGEL K., KLATZO I. Some properties of cultured chick skeletal muscle with particular reference to fibrillation potential. J Cell Comp Physiol. 1959 Jun;53:421–444. doi: 10.1002/jcp.1030530307. [DOI] [PubMed] [Google Scholar]
  19. LILEY A. W. An investigation of spontaneous activity at the neuromuscular junction of the rat. J Physiol. 1956 Jun 28;132(3):650–666. doi: 10.1113/jphysiol.1956.sp005555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lomo T., Rosenthal J. Control of ACh sensitivity by muscle activity in the rat. J Physiol. 1972 Mar;221(2):493–513. doi: 10.1113/jphysiol.1972.sp009764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. MILEDI R., TROWELL O. A. Acetylcholine sensitivity of rat diaphragm maintained in organ culture. Nature. 1962 Jun 9;194:981–982. doi: 10.1038/194981a0. [DOI] [PubMed] [Google Scholar]
  22. MILEDI R. The acetylcholine sensitivity of frog muscle fibres after complete or partial devervation. J Physiol. 1960 Apr;151:1–23. [PMC free article] [PubMed] [Google Scholar]
  23. McArdle J. J., Albuquerque E. X. A study of the reinnervation of fast and slow mammalian muscles. J Gen Physiol. 1973 Jan;61(1):1–23. doi: 10.1085/jgp.61.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Merrill E. G., Ainsworth A. Glass-coated platinum-plated tungsten microelectrodes. Med Biol Eng. 1972 Sep;10(5):662–672. doi: 10.1007/BF02476084. [DOI] [PubMed] [Google Scholar]
  25. Miledi R., Slater C. R. Electrophysiology and electron-microscopy of rat neuromuscular junctions after nerve degeneration. Proc R Soc Lond B Biol Sci. 1968 Feb 27;169(1016):289–306. doi: 10.1098/rspb.1968.0012. [DOI] [PubMed] [Google Scholar]
  26. NARAHASHI T., MOORE J. W., SCOTT W. R. TETRODOTOXIN BLOCKAGE OF SODIUM CONDUCTANCE INCREASE IN LOBSTER GIANT AXONS. J Gen Physiol. 1964 May;47:965–974. doi: 10.1085/jgp.47.5.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Redfern P., Thesleff S. Action potential generation in denervated rat skeletal muscle. II. The action of tetrodotoxin. Acta Physiol Scand. 1971 May;82(1):70–78. doi: 10.1111/j.1748-1716.1971.tb04943.x. [DOI] [PubMed] [Google Scholar]
  28. Vyskocil F., Moravec J., Janský L. Resting state of the myoneural junction in a hibernator. Brain Res. 1971 Nov;34(2):381–384. doi: 10.1016/0006-8993(71)90291-5. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES