Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells

Ming Wei Lin, Ya Jean Wang, Shiuh Inn Liu, An An Lin, Yi Ching Lo, Sheng-Nan Wu

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The effects of aconitine (ACO), a highly toxic alkaloid, on ion currents in differentiated NG108-15 neuronal cells were investigated in this study. ACO (0.3-30 μM) suppressed the amplitude of delayed rectifier K+ current (IK(DR)) in a concentration-dependent manner with an IC50 value of 3.1 μM. The presence of ACO enhanced the rate and extent of IK(DR) inactivation, although it had no effect on the initial activation phase of IK(DR). It could shift the inactivation curve of IK(DR) to a hyperpolarized potential with no change in the slope factor. Cumulative inactivation for IK(DR) was also enhanced by ACO. Orphenadrine (30 μM) or methyllycaconitine (30 μM) slightly suppressed IK(DR) without modifying current decay. ACO (10 μM) had an inhibitory effect on voltage-dependent Na+ current (INa). Under current-clamp recordings, ACO increased the firing and widening of action potentials in these cells. With the aid of the minimal binding scheme, the ACO actions on IK(DR) was quantitatively provided with a dissociation constant of 0.6 μM. A modeled cell was designed to duplicate its inhibitory effect on spontaneous pacemaking. ACO also blocked IK(DR) in neuroblastoma SH-SY5Y cells. Taken together, the experimental data and simulations show that ACO can block delayed rectifier K+ channels of neurons in a concentration- and state-dependent manner. Changes in action potentials induced by ACO in neurons in vivo can be explained mainly by its blocking actions on IK(DR) and INa.

Original languageEnglish
Pages (from-to)912-923
Number of pages12
JournalNeuropharmacology
Volume54
Issue number6
DOIs
Publication statusPublished - 2008 May 1

Fingerprint

Aconitine
Action Potentials
Orphenadrine
Neurons
Poisons
Neuroblastoma
Alkaloids
Inhibitory Concentration 50

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Lin, Ming Wei ; Wang, Ya Jean ; Liu, Shiuh Inn ; Lin, An An ; Lo, Yi Ching ; Wu, Sheng-Nan. / Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells. In: Neuropharmacology. 2008 ; Vol. 54, No. 6. pp. 912-923.
@article{e66b155c01ab4360a54a76f3a1969c3d,
title = "Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells",
abstract = "The effects of aconitine (ACO), a highly toxic alkaloid, on ion currents in differentiated NG108-15 neuronal cells were investigated in this study. ACO (0.3-30 μM) suppressed the amplitude of delayed rectifier K+ current (IK(DR)) in a concentration-dependent manner with an IC50 value of 3.1 μM. The presence of ACO enhanced the rate and extent of IK(DR) inactivation, although it had no effect on the initial activation phase of IK(DR). It could shift the inactivation curve of IK(DR) to a hyperpolarized potential with no change in the slope factor. Cumulative inactivation for IK(DR) was also enhanced by ACO. Orphenadrine (30 μM) or methyllycaconitine (30 μM) slightly suppressed IK(DR) without modifying current decay. ACO (10 μM) had an inhibitory effect on voltage-dependent Na+ current (INa). Under current-clamp recordings, ACO increased the firing and widening of action potentials in these cells. With the aid of the minimal binding scheme, the ACO actions on IK(DR) was quantitatively provided with a dissociation constant of 0.6 μM. A modeled cell was designed to duplicate its inhibitory effect on spontaneous pacemaking. ACO also blocked IK(DR) in neuroblastoma SH-SY5Y cells. Taken together, the experimental data and simulations show that ACO can block delayed rectifier K+ channels of neurons in a concentration- and state-dependent manner. Changes in action potentials induced by ACO in neurons in vivo can be explained mainly by its blocking actions on IK(DR) and INa.",
author = "Lin, {Ming Wei} and Wang, {Ya Jean} and Liu, {Shiuh Inn} and Lin, {An An} and Lo, {Yi Ching} and Sheng-Nan Wu",
year = "2008",
month = "5",
day = "1",
doi = "10.1016/j.neuropharm.2008.01.009",
language = "English",
volume = "54",
pages = "912--923",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
number = "6",

}

Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells. / Lin, Ming Wei; Wang, Ya Jean; Liu, Shiuh Inn; Lin, An An; Lo, Yi Ching; Wu, Sheng-Nan.

In: Neuropharmacology, Vol. 54, No. 6, 01.05.2008, p. 912-923.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells

AU - Lin, Ming Wei

AU - Wang, Ya Jean

AU - Liu, Shiuh Inn

AU - Lin, An An

AU - Lo, Yi Ching

AU - Wu, Sheng-Nan

PY - 2008/5/1

Y1 - 2008/5/1

N2 - The effects of aconitine (ACO), a highly toxic alkaloid, on ion currents in differentiated NG108-15 neuronal cells were investigated in this study. ACO (0.3-30 μM) suppressed the amplitude of delayed rectifier K+ current (IK(DR)) in a concentration-dependent manner with an IC50 value of 3.1 μM. The presence of ACO enhanced the rate and extent of IK(DR) inactivation, although it had no effect on the initial activation phase of IK(DR). It could shift the inactivation curve of IK(DR) to a hyperpolarized potential with no change in the slope factor. Cumulative inactivation for IK(DR) was also enhanced by ACO. Orphenadrine (30 μM) or methyllycaconitine (30 μM) slightly suppressed IK(DR) without modifying current decay. ACO (10 μM) had an inhibitory effect on voltage-dependent Na+ current (INa). Under current-clamp recordings, ACO increased the firing and widening of action potentials in these cells. With the aid of the minimal binding scheme, the ACO actions on IK(DR) was quantitatively provided with a dissociation constant of 0.6 μM. A modeled cell was designed to duplicate its inhibitory effect on spontaneous pacemaking. ACO also blocked IK(DR) in neuroblastoma SH-SY5Y cells. Taken together, the experimental data and simulations show that ACO can block delayed rectifier K+ channels of neurons in a concentration- and state-dependent manner. Changes in action potentials induced by ACO in neurons in vivo can be explained mainly by its blocking actions on IK(DR) and INa.

AB - The effects of aconitine (ACO), a highly toxic alkaloid, on ion currents in differentiated NG108-15 neuronal cells were investigated in this study. ACO (0.3-30 μM) suppressed the amplitude of delayed rectifier K+ current (IK(DR)) in a concentration-dependent manner with an IC50 value of 3.1 μM. The presence of ACO enhanced the rate and extent of IK(DR) inactivation, although it had no effect on the initial activation phase of IK(DR). It could shift the inactivation curve of IK(DR) to a hyperpolarized potential with no change in the slope factor. Cumulative inactivation for IK(DR) was also enhanced by ACO. Orphenadrine (30 μM) or methyllycaconitine (30 μM) slightly suppressed IK(DR) without modifying current decay. ACO (10 μM) had an inhibitory effect on voltage-dependent Na+ current (INa). Under current-clamp recordings, ACO increased the firing and widening of action potentials in these cells. With the aid of the minimal binding scheme, the ACO actions on IK(DR) was quantitatively provided with a dissociation constant of 0.6 μM. A modeled cell was designed to duplicate its inhibitory effect on spontaneous pacemaking. ACO also blocked IK(DR) in neuroblastoma SH-SY5Y cells. Taken together, the experimental data and simulations show that ACO can block delayed rectifier K+ channels of neurons in a concentration- and state-dependent manner. Changes in action potentials induced by ACO in neurons in vivo can be explained mainly by its blocking actions on IK(DR) and INa.

UR - http://www.scopus.com/inward/record.url?scp=41949130248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41949130248&partnerID=8YFLogxK

U2 - 10.1016/j.neuropharm.2008.01.009

DO - 10.1016/j.neuropharm.2008.01.009

M3 - Article

C2 - 18336846

AN - SCOPUS:41949130248

VL - 54

SP - 912

EP - 923

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 6

ER -