Effects of midazolam on ion currents and membrane potential in differentiated motor neuron-like NSC-34 and NG108-15 cells

Edmund Cheung So, King Chuen Wu, Feng Chen Kao, Sheng-Nan Wu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Midazolam (MDL) was known to act through stimulation of benzodiazepine receptors (GABA). Whether midazolam affects ion currents and membrane potential in neurons remains largely unclear. Electrophysiological studies of midazolam actions were performed in differentiated motor neuron-like (NSC-34 and NG108-15) cells. Midazolam suppressed the amplitude of delayed rectifier K+ current (IK(DR)) in a time- and concentration-dependent manner with an IC50 value of 10.4 μM. Addition of midazolam was noted to enhance the rate of IK(DR) inactivation. On the basis of minimal binding scheme, midazolam-induced block of IK(DR) was quantitatively provided with a dissociation constant of 9.8 μM. Recovery of I K(DR) from inactivation in the presence of midazolam was fitted by a single exponential. midazolam had no effect on M-type or erg-mediated K + current in these cells. Midazaolam (30 μM) suppressed the peak amplitude of voltage-gated Na+ current (INa) with no change in the current-voltage relationships of this current. Inactivation kinetics of INa remained unaltered in the presence of this agent. In current-clamp configuration, midazolam (30 μM) prolonged the duration of action potentials (APs) and reduce AP amplitude. Similarly, in differentiated NG108-15 cells, the exposure to midazolam also suppressed IK(DR) with a concomitant increase in current inactivation. Midazolam can act as an open-channel blocker of delayed-rectifier K+ channels in these cells. The synergistic blocking effects on IK(DR) and INa may contribute to the underlying mechanisms through which midazolam affects neuronal function in vivo.

Original languageEnglish
Pages (from-to)152-160
Number of pages9
JournalEuropean Journal of Pharmacology
Volume724
Issue number1
DOIs
Publication statusPublished - 2014 Feb 5

Fingerprint

Midazolam
Motor Neurons
Membrane Potentials
Ions
Action Potentials
GABA-A Receptors
Inhibitory Concentration 50

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

@article{8aa3ec035406482392c3e16cb394b8aa,
title = "Effects of midazolam on ion currents and membrane potential in differentiated motor neuron-like NSC-34 and NG108-15 cells",
abstract = "Midazolam (MDL) was known to act through stimulation of benzodiazepine receptors (GABA). Whether midazolam affects ion currents and membrane potential in neurons remains largely unclear. Electrophysiological studies of midazolam actions were performed in differentiated motor neuron-like (NSC-34 and NG108-15) cells. Midazolam suppressed the amplitude of delayed rectifier K+ current (IK(DR)) in a time- and concentration-dependent manner with an IC50 value of 10.4 μM. Addition of midazolam was noted to enhance the rate of IK(DR) inactivation. On the basis of minimal binding scheme, midazolam-induced block of IK(DR) was quantitatively provided with a dissociation constant of 9.8 μM. Recovery of I K(DR) from inactivation in the presence of midazolam was fitted by a single exponential. midazolam had no effect on M-type or erg-mediated K + current in these cells. Midazaolam (30 μM) suppressed the peak amplitude of voltage-gated Na+ current (INa) with no change in the current-voltage relationships of this current. Inactivation kinetics of INa remained unaltered in the presence of this agent. In current-clamp configuration, midazolam (30 μM) prolonged the duration of action potentials (APs) and reduce AP amplitude. Similarly, in differentiated NG108-15 cells, the exposure to midazolam also suppressed IK(DR) with a concomitant increase in current inactivation. Midazolam can act as an open-channel blocker of delayed-rectifier K+ channels in these cells. The synergistic blocking effects on IK(DR) and INa may contribute to the underlying mechanisms through which midazolam affects neuronal function in vivo.",
author = "So, {Edmund Cheung} and Wu, {King Chuen} and Kao, {Feng Chen} and Sheng-Nan Wu",
year = "2014",
month = "2",
day = "5",
doi = "10.1016/j.ejphar.2013.12.034",
language = "English",
volume = "724",
pages = "152--160",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1",

}

Effects of midazolam on ion currents and membrane potential in differentiated motor neuron-like NSC-34 and NG108-15 cells. / So, Edmund Cheung; Wu, King Chuen; Kao, Feng Chen; Wu, Sheng-Nan.

In: European Journal of Pharmacology, Vol. 724, No. 1, 05.02.2014, p. 152-160.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of midazolam on ion currents and membrane potential in differentiated motor neuron-like NSC-34 and NG108-15 cells

AU - So, Edmund Cheung

AU - Wu, King Chuen

AU - Kao, Feng Chen

AU - Wu, Sheng-Nan

PY - 2014/2/5

Y1 - 2014/2/5

N2 - Midazolam (MDL) was known to act through stimulation of benzodiazepine receptors (GABA). Whether midazolam affects ion currents and membrane potential in neurons remains largely unclear. Electrophysiological studies of midazolam actions were performed in differentiated motor neuron-like (NSC-34 and NG108-15) cells. Midazolam suppressed the amplitude of delayed rectifier K+ current (IK(DR)) in a time- and concentration-dependent manner with an IC50 value of 10.4 μM. Addition of midazolam was noted to enhance the rate of IK(DR) inactivation. On the basis of minimal binding scheme, midazolam-induced block of IK(DR) was quantitatively provided with a dissociation constant of 9.8 μM. Recovery of I K(DR) from inactivation in the presence of midazolam was fitted by a single exponential. midazolam had no effect on M-type or erg-mediated K + current in these cells. Midazaolam (30 μM) suppressed the peak amplitude of voltage-gated Na+ current (INa) with no change in the current-voltage relationships of this current. Inactivation kinetics of INa remained unaltered in the presence of this agent. In current-clamp configuration, midazolam (30 μM) prolonged the duration of action potentials (APs) and reduce AP amplitude. Similarly, in differentiated NG108-15 cells, the exposure to midazolam also suppressed IK(DR) with a concomitant increase in current inactivation. Midazolam can act as an open-channel blocker of delayed-rectifier K+ channels in these cells. The synergistic blocking effects on IK(DR) and INa may contribute to the underlying mechanisms through which midazolam affects neuronal function in vivo.

AB - Midazolam (MDL) was known to act through stimulation of benzodiazepine receptors (GABA). Whether midazolam affects ion currents and membrane potential in neurons remains largely unclear. Electrophysiological studies of midazolam actions were performed in differentiated motor neuron-like (NSC-34 and NG108-15) cells. Midazolam suppressed the amplitude of delayed rectifier K+ current (IK(DR)) in a time- and concentration-dependent manner with an IC50 value of 10.4 μM. Addition of midazolam was noted to enhance the rate of IK(DR) inactivation. On the basis of minimal binding scheme, midazolam-induced block of IK(DR) was quantitatively provided with a dissociation constant of 9.8 μM. Recovery of I K(DR) from inactivation in the presence of midazolam was fitted by a single exponential. midazolam had no effect on M-type or erg-mediated K + current in these cells. Midazaolam (30 μM) suppressed the peak amplitude of voltage-gated Na+ current (INa) with no change in the current-voltage relationships of this current. Inactivation kinetics of INa remained unaltered in the presence of this agent. In current-clamp configuration, midazolam (30 μM) prolonged the duration of action potentials (APs) and reduce AP amplitude. Similarly, in differentiated NG108-15 cells, the exposure to midazolam also suppressed IK(DR) with a concomitant increase in current inactivation. Midazolam can act as an open-channel blocker of delayed-rectifier K+ channels in these cells. The synergistic blocking effects on IK(DR) and INa may contribute to the underlying mechanisms through which midazolam affects neuronal function in vivo.

UR - http://www.scopus.com/inward/record.url?scp=84892410873&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892410873&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2013.12.034

DO - 10.1016/j.ejphar.2013.12.034

M3 - Article

VL - 724

SP - 152

EP - 160

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1

ER -