Menthol increases human glioblastoma intracellular Ca2+, BK channel activity and cell migration

Robert Wondergem, Jeremy W. Bartley

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

This study examined the effect of menthol, an agonist for transient receptor potential melastatin 8 (TRPM8) ion channels, to increase intracellular Ca2+ concentration, [Ca2+]i, in human glioblastoma cells (DBTRG cells), which resulted in activation of the large-conductance Ca2+-activated K+ membrane ion channels (BK channels). Voltage ramps applied over 300 ms from -100 to 100 mV resulted in membrane currents with marked inwardly- and outwardly-rectifying components. Paxilline (2 M) abolished the outwardly-rectifying current. Outwardly-rectifying on-cell patch currents were increased markedly by menthol (100 M) added to the bath. The estimated on-cell conductance of these channels was 253 pS. Kinetic analysis showed that added menthol increased channel open probability and mean open frequency after 5 min. In a similar time course menthol increased [Ca 2+]i, and this increase was abolished either by added paxilline, tetraethylammonium ion or by Ca2+-free external solution. Finally, menthol stimulated the rate of DBTRG cell migration into scratch wounds made in confluent cells, and this also was inhibited by paxilline or by tetraethylammonium ion. We conclude that menthol, a TRPM8 agonist, increases DBTRG cell [Ca2+]ithat in turn activates membrane BK ion channels. Inhibition of BK channels by paxilline reverses menthol-stimulated increase of [Ca2+]iand of cell migration. Thus, BK channels function to maintain elevations in [Ca2+]ineeded to sustain increases in DBTRG cell migration.

Original languageEnglish (US)
Article number90
JournalJournal of Biomedical Science
Volume16
Issue number1
DOIs
StatePublished - Nov 9 2009

Fingerprint

Menthol
Large-Conductance Calcium-Activated Potassium Channels
Glioblastoma
Cell Movement
Ion Channels
Tetraethylammonium
Membranes
Architectural Accessibility
Baths
Chemical activation
Kinetics
paxilline
Wounds and Injuries
Electric potential

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

Cite this

Menthol increases human glioblastoma intracellular Ca2+, BK channel activity and cell migration. / Wondergem, Robert; Bartley, Jeremy W.

In: Journal of Biomedical Science, Vol. 16, No. 1, 90, 09.11.2009.

Research output: Contribution to journalArticle

@article{0d058c44a98042b8ad047e04b191d217,
title = "Menthol increases human glioblastoma intracellular Ca2+, BK channel activity and cell migration",
abstract = "This study examined the effect of menthol, an agonist for transient receptor potential melastatin 8 (TRPM8) ion channels, to increase intracellular Ca2+ concentration, [Ca2+]i, in human glioblastoma cells (DBTRG cells), which resulted in activation of the large-conductance Ca2+-activated K+ membrane ion channels (BK channels). Voltage ramps applied over 300 ms from -100 to 100 mV resulted in membrane currents with marked inwardly- and outwardly-rectifying components. Paxilline (2 M) abolished the outwardly-rectifying current. Outwardly-rectifying on-cell patch currents were increased markedly by menthol (100 M) added to the bath. The estimated on-cell conductance of these channels was 253 pS. Kinetic analysis showed that added menthol increased channel open probability and mean open frequency after 5 min. In a similar time course menthol increased [Ca 2+]i, and this increase was abolished either by added paxilline, tetraethylammonium ion or by Ca2+-free external solution. Finally, menthol stimulated the rate of DBTRG cell migration into scratch wounds made in confluent cells, and this also was inhibited by paxilline or by tetraethylammonium ion. We conclude that menthol, a TRPM8 agonist, increases DBTRG cell [Ca2+]ithat in turn activates membrane BK ion channels. Inhibition of BK channels by paxilline reverses menthol-stimulated increase of [Ca2+]iand of cell migration. Thus, BK channels function to maintain elevations in [Ca2+]ineeded to sustain increases in DBTRG cell migration.",
author = "Robert Wondergem and Bartley, {Jeremy W.}",
year = "2009",
month = "11",
day = "9",
doi = "10.1186/1423-0127-16-90",
language = "English (US)",
volume = "16",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Menthol increases human glioblastoma intracellular Ca2+, BK channel activity and cell migration

AU - Wondergem, Robert

AU - Bartley, Jeremy W.

PY - 2009/11/9

Y1 - 2009/11/9

N2 - This study examined the effect of menthol, an agonist for transient receptor potential melastatin 8 (TRPM8) ion channels, to increase intracellular Ca2+ concentration, [Ca2+]i, in human glioblastoma cells (DBTRG cells), which resulted in activation of the large-conductance Ca2+-activated K+ membrane ion channels (BK channels). Voltage ramps applied over 300 ms from -100 to 100 mV resulted in membrane currents with marked inwardly- and outwardly-rectifying components. Paxilline (2 M) abolished the outwardly-rectifying current. Outwardly-rectifying on-cell patch currents were increased markedly by menthol (100 M) added to the bath. The estimated on-cell conductance of these channels was 253 pS. Kinetic analysis showed that added menthol increased channel open probability and mean open frequency after 5 min. In a similar time course menthol increased [Ca 2+]i, and this increase was abolished either by added paxilline, tetraethylammonium ion or by Ca2+-free external solution. Finally, menthol stimulated the rate of DBTRG cell migration into scratch wounds made in confluent cells, and this also was inhibited by paxilline or by tetraethylammonium ion. We conclude that menthol, a TRPM8 agonist, increases DBTRG cell [Ca2+]ithat in turn activates membrane BK ion channels. Inhibition of BK channels by paxilline reverses menthol-stimulated increase of [Ca2+]iand of cell migration. Thus, BK channels function to maintain elevations in [Ca2+]ineeded to sustain increases in DBTRG cell migration.

AB - This study examined the effect of menthol, an agonist for transient receptor potential melastatin 8 (TRPM8) ion channels, to increase intracellular Ca2+ concentration, [Ca2+]i, in human glioblastoma cells (DBTRG cells), which resulted in activation of the large-conductance Ca2+-activated K+ membrane ion channels (BK channels). Voltage ramps applied over 300 ms from -100 to 100 mV resulted in membrane currents with marked inwardly- and outwardly-rectifying components. Paxilline (2 M) abolished the outwardly-rectifying current. Outwardly-rectifying on-cell patch currents were increased markedly by menthol (100 M) added to the bath. The estimated on-cell conductance of these channels was 253 pS. Kinetic analysis showed that added menthol increased channel open probability and mean open frequency after 5 min. In a similar time course menthol increased [Ca 2+]i, and this increase was abolished either by added paxilline, tetraethylammonium ion or by Ca2+-free external solution. Finally, menthol stimulated the rate of DBTRG cell migration into scratch wounds made in confluent cells, and this also was inhibited by paxilline or by tetraethylammonium ion. We conclude that menthol, a TRPM8 agonist, increases DBTRG cell [Ca2+]ithat in turn activates membrane BK ion channels. Inhibition of BK channels by paxilline reverses menthol-stimulated increase of [Ca2+]iand of cell migration. Thus, BK channels function to maintain elevations in [Ca2+]ineeded to sustain increases in DBTRG cell migration.

UR - http://www.scopus.com/inward/record.url?scp=70350638630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350638630&partnerID=8YFLogxK

U2 - 10.1186/1423-0127-16-90

DO - 10.1186/1423-0127-16-90

M3 - Article

C2 - 19778436

AN - SCOPUS:70350638630

VL - 16

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

IS - 1

M1 - 90

ER -