The effect of anthopleurin-A on crayfish giant axon

P. A. Low, C. H. Wu, T. Narahashi

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The effects of anthopleurin-A (AP-A) isolated from the sea anemone Anthopleura xanthogrammica on resting and action potentials and membrane currents were studied on crayfish giant axons using the intracellular microelectrode and voltage clamp techniques. At low concentrations of AP-A (10-8 M) the resting potential underwent cycles of spontaneous depolarization followed by repolarization, producing an undulating pattern. Repetitive firing occurred both spontaneously and in response to a single stimulus. The rate of rise, amplitude and initial falling phase of the action potential were unaffected, but the lateral falling phase was replaced by a long plateau. At higher concentrations of AP-A (10-7-10-6 M), depolarizations of 10 to 40 mV were seen, which were not followed by repolarizations. Both the depolarization and undulating pattern were antagonized by 300 nM tetrodotoxin, 10 to 20 mM procaine and van Harreveld's solution in which sodium concentration was reduced to 1 mM. These findings indicate that the ionic channel responsible for these perturbations is that of sodium. In contrast to the effects of neurotoxin II of Anemonia sulcata (ATX II), prior treatment with tetrodotoxin or procaine did not affect subsequent interaction of AP-A with its receptor. As the tetrodotoxin effect was reversed on washing, the action potential returned and had a marked plateau typical of AP-A effect. The same observations were made with procaine. Membrane currents were measured on the axons in which potassium channels were blocked with 2 mM 4-aminopyridine. The kinetics of sodium activation appeared normal, but inactivation was markedly slowed in the presence of 10-7 M AP-A. Sodium tail currents, after application of AP-A, were increased in amplitude and modified in time course, having an additional component with long time course of recovery. The peak current was slightly reduced in amplitude after AP-A application with the reversal potential unaffected. However, steady-state currents, reflecting mainly altered sodium channels were greatly increased following AP-A treatment.

Original languageEnglish (US)
Pages (from-to)417-421
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume210
Issue number3
StatePublished - 1979

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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