- 作者: Robert Wondergem; Jeremy W. Bartley
- 作者服務機構: Department of Physiology, James H. Quillen College of Medicine, East Tennessee State University, Tennessee, USA
- 中文摘要: --
- 英文摘要:
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 outwardlyrectifying
components. Paxilline (2 μM) abolished the outwardly-rectifying
current. Outwardly-rectifying on-cell patch currents were increased markedly by
menthol (100 μM) 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 [Ca2+]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+]i that in turn activates membrane BK ion channels.
Inhibition of BK channels by paxilline reverses menthol-stimulated increase of
[Ca2+]i and of cell migration. Thus, BK channels function to maintain elevations in
[Ca2+]i needed to sustain increases in DBTRG cell migration. - 中文關鍵字: --
- 英文關鍵字: --