Elektrophysiologische Charakterisierung der Effekte von Menthol auf die hypothalamische Mauszelllinie GT1 mit der Patch-Clamp-Technik
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Philipps-Universität Marburg
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Abstract
It is well known that menthol evokes a sensation of cold when applied to skin or mucosa. The
underlying ionic mechanisms, however, are still under debate. Blockade of Ca2+ currents with
reduction of Ca2+ dependent K+ currents have been discussed. Recordings from DRG neurons
clearly demonstrated menthol induced activation of TRPM8 (CMR1) ion channels and
depolarisation of the cell membrane caused by Ca2+ influx. Moreover, recent studies suggest
multiple actions of menthol including, for example, excitation of TRPV3 and inhibition of
TRPA1 (ANKTM1) channels.
Here menthol was used as an agent to examine desensitization effects on a hypothalamic
GT1-7 neuronal cell line by using PCR, Ca2+-Imaging and whole cell patch clamp techniques.
PCR studies verified the expression of TRPM8 mRNA, but Ca2+-Imaging does not show an
increase of intracellular Ca2+ during menthol application. The patch-clamp studies demonstrated
a pronounced reduction of an outward current which cannot be explained by the conventional
assumptions about the action of menthol via TRP channels. The data point to a dose
dependent inhibition of voltage-dependent K+ channels which is completely reversible. Recordings
made under extracellular K+ concentration of 140 mM support this concept. Menthol
effects occurred also in Ca2+ free bath solution. To examine whether menthol affects further
currents besides K+, Na+ currents were isolated and are not affected by menthol.
The two major voltage dependent K+-currents (delayed rectifier of A- and DR-current)
were identified according to their different activation characteristics. Menthol blocks the majority
of DR-currents, while the A-currents persist. In a dose response curve the EC50 value
of all blocked outward-currents is 380 μM.
As menthol blocks the DR-type K+ current, the shape of APs might be changed. Functionally,
this could lead to different firing rates and patterns, which is thought to influence hormone
release.
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Created: 2009Issued: 2010-01-26Updated: 2011-08-10
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Action potentialVoltage dependent K+ channelsWhole-cellTRPM8AktionspotentialGnRHTRPM8
DFG-subjects
Gonadotropin-ReleasinghormonSpannungskontrollierter Ionenkanal
DDC-Numbers
610
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Wegner, Sven: Elektrophysiologische Charakterisierung der Effekte von Menthol auf die hypothalamische Mauszelllinie GT1 mit der Patch-Clamp-Technik. : Philipps-Universität Marburg 2010-01-26. DOI: https://doi.org/10.17192/z2009.0793.
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This item has been published with the following license: In Copyright