Characterization of an inward current elicited by edrophonium in physically isolated and internally perfused Aplysia neurons

Y. Oyama, W. M. King, Charles Allen, N. Hori, D. O. Carpenter

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We have studied the ionic and pharmacological properties of an inward current elicited by edrophonium, a cholinesterase inhibitor, on physically isolated and internally perfused Aplysia neurons using the voltage clamp, internal perfusion and rapid external perfusion techniques. The current amplitude was dependent on the external Na concentration [(Na)o] in an almost linear manner. However, complete replacement of (Na)o with Tris or sucrose failed to abolish the current. Internal application of Na [increased (Na)i] reduced the current amplitude. In normal (Na)o, changing (Ca)o (both increases and decreases in (Ca)o) reduced the current amplitude. In the sucrose-substituted (Na)o-free condition, edrophonium still could cause a small current (less than 5% of the control). However, an increased (Ca)o did not augment this residual current. Cs and Li carried the edrophonium-activated current when substituted for (Na)o. With sucrose-substituted Na-free sea water outside, edrophonium elicited an outward current when the neuron was internally perfused with Cs, but not when the neuron was internally perfused with K. Therefore, it is unlikely that K is permeant. External application of tetrodotoxin, a blocker of voltage-dependent Na channels, external application of Cd and internal application of F did not affect the current. The edrophonium response was most sensitive to strychnine, which was about 10 times more potent than d-tubocurarine. Hexamethonium, however, had no effect. The local anesthetics, lidocaine and procaine, inhibited the response over the same concentration range as d-tubocurarine. We conclude that edrophonium opens a monocationic channel (presumably a type of Na channel) which is sensitive to (Ca)o. The mechanism of activation is distinct from the acetylcholine receptor-channel complex and the edrophonium response (receptor, channel or both) is relatively non-specifically blocked by several drugs.

Original languageEnglish (US)
Pages (from-to)124-132
Number of pages9
JournalBrain Research
Volume463
Issue number1
DOIs
StatePublished - Oct 25 1988
Externally publishedYes

Fingerprint

Edrophonium
Aplysia
Neurons
Sucrose
Tubocurarine
Perfusion
Strychnine
Hexamethonium
Procaine
Cholinesterase Inhibitors
Tetrodotoxin
Seawater
Cholinergic Receptors
Lidocaine
Local Anesthetics
Pharmacology

Keywords

  • Aplysia neuron
  • Concentration clamp
  • Edrophonium
  • Intracellular perfusion
  • Sodium current

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Characterization of an inward current elicited by edrophonium in physically isolated and internally perfused Aplysia neurons. / Oyama, Y.; King, W. M.; Allen, Charles; Hori, N.; Carpenter, D. O.

In: Brain Research, Vol. 463, No. 1, 25.10.1988, p. 124-132.

Research output: Contribution to journalArticle

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abstract = "We have studied the ionic and pharmacological properties of an inward current elicited by edrophonium, a cholinesterase inhibitor, on physically isolated and internally perfused Aplysia neurons using the voltage clamp, internal perfusion and rapid external perfusion techniques. The current amplitude was dependent on the external Na concentration [(Na)o] in an almost linear manner. However, complete replacement of (Na)o with Tris or sucrose failed to abolish the current. Internal application of Na [increased (Na)i] reduced the current amplitude. In normal (Na)o, changing (Ca)o (both increases and decreases in (Ca)o) reduced the current amplitude. In the sucrose-substituted (Na)o-free condition, edrophonium still could cause a small current (less than 5{\%} of the control). However, an increased (Ca)o did not augment this residual current. Cs and Li carried the edrophonium-activated current when substituted for (Na)o. With sucrose-substituted Na-free sea water outside, edrophonium elicited an outward current when the neuron was internally perfused with Cs, but not when the neuron was internally perfused with K. Therefore, it is unlikely that K is permeant. External application of tetrodotoxin, a blocker of voltage-dependent Na channels, external application of Cd and internal application of F did not affect the current. The edrophonium response was most sensitive to strychnine, which was about 10 times more potent than d-tubocurarine. Hexamethonium, however, had no effect. The local anesthetics, lidocaine and procaine, inhibited the response over the same concentration range as d-tubocurarine. We conclude that edrophonium opens a monocationic channel (presumably a type of Na channel) which is sensitive to (Ca)o. The mechanism of activation is distinct from the acetylcholine receptor-channel complex and the edrophonium response (receptor, channel or both) is relatively non-specifically blocked by several drugs.",
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N2 - We have studied the ionic and pharmacological properties of an inward current elicited by edrophonium, a cholinesterase inhibitor, on physically isolated and internally perfused Aplysia neurons using the voltage clamp, internal perfusion and rapid external perfusion techniques. The current amplitude was dependent on the external Na concentration [(Na)o] in an almost linear manner. However, complete replacement of (Na)o with Tris or sucrose failed to abolish the current. Internal application of Na [increased (Na)i] reduced the current amplitude. In normal (Na)o, changing (Ca)o (both increases and decreases in (Ca)o) reduced the current amplitude. In the sucrose-substituted (Na)o-free condition, edrophonium still could cause a small current (less than 5% of the control). However, an increased (Ca)o did not augment this residual current. Cs and Li carried the edrophonium-activated current when substituted for (Na)o. With sucrose-substituted Na-free sea water outside, edrophonium elicited an outward current when the neuron was internally perfused with Cs, but not when the neuron was internally perfused with K. Therefore, it is unlikely that K is permeant. External application of tetrodotoxin, a blocker of voltage-dependent Na channels, external application of Cd and internal application of F did not affect the current. The edrophonium response was most sensitive to strychnine, which was about 10 times more potent than d-tubocurarine. Hexamethonium, however, had no effect. The local anesthetics, lidocaine and procaine, inhibited the response over the same concentration range as d-tubocurarine. We conclude that edrophonium opens a monocationic channel (presumably a type of Na channel) which is sensitive to (Ca)o. The mechanism of activation is distinct from the acetylcholine receptor-channel complex and the edrophonium response (receptor, channel or both) is relatively non-specifically blocked by several drugs.

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