Item type:Doctoral Thesis, Open Access

Elektrophysiologische Charakterisierung der Effekte von Menthol auf die hypothalamische Mauszelllinie GT1 mit der Patch-Clamp-Technik

Thumbnail Image

Files

dsw.pdf (3.57 MB)

Date

2010-01-26

Authors

Publisher

Philipps-Universität Marburg
DOI

Supervisors

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.

Review

Metadata

Contributors
Supervisor:
Dates
Created: 2009Issued: 2010-01-26Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2009.0793
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
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2009.0793
show more
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.

License

item.page.license.under-copyright
This item has been published with the following license: In Copyright

Related Items