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4.10 Preise und Publikationen

Diese Dissertationsarbeit wurde unterstützt durch die Europäische Union durch das ‚Net-work of Excellence Biosim, Contract No. LSHB-CT-2004-005137’ sowie durch ein Stipen-dium der Medizinstiftung Marburg. Die Arbeit wurde im Dissertationswettbewerb im Rahmen der ‚Brain Awareness Week 2007’ durch Prof. Dr. Krieg, Prof. Dr. Oertel, Prof. Dr. Pagenste-cher und Prof. Dr. Sure zur besten neurowissenschaftlichen Dissertation der Universität Mar-burg ernannt.

Aus dieser Arbeit gehen einige Poster für Kongresse und Publikationen hervor:

Kongress-Poster

• Wegner S, Wollweber BT, Schneider H, Voigt H, Braun HA. (2006). Menthol effects in whole-cell voltage-clamp recordings of hypothalamic neurons. 2nd BioSim Confer-ence.

• Wollweber BT, Randolf A, Schäfer MKH, Wegner S, Postnova S, Voigt K, Braun HA. (2006). Modulation of Hypothalamic Temperature Sensitivity by Menthol. 2nd BioSim Conference.

• Wollweber BT, Wegner S, Randolf A, Schäfer MKH, Schneider H, Voigt K and Braun HA. (2007). Menthol effects on hypothalamic neurons. 7th Meeting of the German Neuroscience Society.

Publikationen

Wegner S, Schneider H, Braun HA, Voigt K, Wollweber BT. Menthol blocks potassium currents in an immortalized hypothalamic neuronal cell line. Manuskript.

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6 Anhänge

Verzeichnis der verwendeten Abkürzungen

4-AP 4-Aminopyridin

ADP Adenosindiphosphat

AS Aminosäure

ATP Adenosin-5´-triphosphat

BK big conductance K+-channels

CC Current clamp

CMR1 Cold and menthol receptor 1 (= TRPM8)

Cox2 Cyclooxygenase 2

CpG Cytosine paired Guanine

CRH Corticotropin-Releasing Hormone

Da Dalton

DAG Diacylglycerol

DMEM Dulbecco's Modified Eagle Medium DMSO Dimethylsulfoxid

DNA Desoxyribonuklein Acid

D-PBS Dulbecco's Phosphate Buffered Saline EDTA Ethylendiamintetraacetat

EGTA Ethylenglycol-bis(ß-aminoethylether) tetraacetic acid

ER endoplasmatisches Retikulum

FCS Fetal calf serum

FSH Follikelstimulierendes Hormon GABA Gamma-aminobutyric-acid

GDP Guanosin diphosphate

GnRH Gonadotropin releasing hormone

GTP Guanosin triphosphate

GPCR G-Protein gekoppelten Rezeptor

GT1 GnRH produzierende SV40 T-antigen transfizierte Zelllinie 1 HUVEC Human umbilical vein endothelal cell

I.E. Internationale Einheit

LH Luteinisierendes Hormon

IKCa Intermediate conductance Ca2+ dependent K+ channel (= SK4) IP3 Inositol-1,4,5-triphosphat

LPS Lipopolysaccarid

LTB4 Leukotrien B4

MW molecular weight

NADPH reduced nicotinamid adenine dinucleotid phosphate

OHC Outer hair cell

OVLT Organum vasculosum laminae terminalis

PAG Periaqueductal gray PGE2 / PGI2 Prostaglandin E2 / I2

PIP2 Phosphatidylinositol-4,5-bisphosphat

PKC Proteinkinase C

PLC Phospholipase C

mPOA Medial Preoptic Area

RES Reticuloendothelial system (= MPS) RMP Ruhemembranpotential RVD Regularory volume decrease

SK Small conductance potassium channel

TEA Tetraethylamonium

TMD Transmembran Domäne

TNF-α Tumor necrosis factor-α

TRPC Transient receptor potential classical type TRPM8 Transient receptor potential melanostatin 8 TRPV1 Transient receptor potential vanilloid type 1

TTX Tetrodotoxin

VC Voltage clamp

Nicht aufgeführt sind:

• Die Formelzeichen des Internationalen Einheitensystems (SI, Le Système

international d'unités) und deren abgeleitete Einheiten. Abkürzungen in Formeln sind dort angegeben.

• Die Abkürzungen für chemische Elemente. Sie entsprechen den Angaben des Periodensystems der Elemente nach der International Union of Pure and Applied Chemistry (IUPAC).

• Allgemein gebräuchliche Abkürzungen der deutschen Sprache nach dem Duden.

• Abkürzungen, die im Text erläutert sind.

Abbildungs- und Tabellenverzeichnis

Alle Abbildungen sind, sofern nicht anders in der Legende beschrieben, eigenständig von mir erstellt worden.

Abbildungen:

Abbildung 1.1 Regulation von Hunger und Sattheit im Hypothalamus ... 6

Abbildung 1.2 Regulation der GnRH-Ausschüttung... 10

Abbildung 1.3 Steuerung der Körpertemperatur, Einzelheiten siehe Text... 13

Abbildung 1.4 Elektrophysiologische Trennung der IK(A)- und IK(DR)-Ströme ... 15

Abbildung 1.5 α-Untereinheit eines spannungsabhänigigen K+-Kanal ... 16

Abbildung 1.6 α-Untereinheit des BKCa-Kanals... 18

Abbildung 1.7 Charakteristische Strom-Spannungskurve eines Kir-Kanals ... 19

Abbildung 1.8 Charakteristischer Na+-Einstrom durch die NaV zu Beginn eines Aktionspotentials... 22

Abbildung 2.1 Neubauer Zählkammer... 26

Abbildung 2.2 Übersicht über den Messstand... 27

Abbildung 2.3 Messkammer ... 28

Abbildung 2.4 Verstärker ... 29

Abbildung 2.5 Testpuls im Programm ‚Oszi’ ... 30

Abbildung 2.6 Messschuh ... 31

Abbildung 2.7 Puller ... 34

Abbildung 2.8 Microforge... 34

Abbildung 2.9 Coating-Stand... 35

Abbildung 2.10 Leckströme ... 39

Abbildung 2.11 Patch-Clamp Konfigurationen ... 40

Abbildung 2.12 Strom-Spannungs-Diagramm mit Umkehrpunkt bei -60 mV... 43

Abbildung 2.13 Doppelkap Protokoll zur Bestimmung der Membrankapazitäten ... 45

Abbildung 2.14 Bestimmung des Membranpotentials anhand eines Strom-Spannungs-Diagramms . 45 Abbildung 2.15 Spannungsklemme... 46

Abbildung 2.16 APs in der Stromklemme... 47

Abbildung 3.1 PCR ... 53

Abbildung 3.2 Ca2+-Imaging der GT1-Zellen... 54

Abbildung 3.3 Hemmung der Auswärtsströme durch Menthol, 4-AP und TEA... 56

Abbildung 3.4 Strom-Spannungs-Diagramme unter Hoch-K+-Badlösung ... 58

Abbildung 3.5 Charakterisierung der K+-Ströme ... 60

Abbildung 3.6 Dosis-Wirkungskurve der Mentholinduzierten Hemmung des Auswärtsstroms ... 61

Abbildung 3.7 Strom-Spannungsdiagramm bei Na+-Isolation... 63

Abbildung 3.8 Messungen in Ca2+ freier Badlösung ... 65

Abbildung 3.9 Bestimmung der Leitfähigkeit eines Einzelkanals ... 66

Abbildung 3.10 Fotos der GT1-7 Zellen in verschiedenen Zuständen... 67

Abbildung 4.1 Kinetiken und Modifizierung der KV1-Kanäle... 71

Abbildung 4.3 Applikation von 3 mM Menthol ... 73

Tabellen:

Tabelle 1.1 Übersicht über die Blocker der verschiedenen K+-Kanäle ... 21 Tabelle 2.1 Intra- und extrazelluläre Konzentrationen sowie die Nernstpotentiale der wichtigsten Ionen

... 42 Tabelle 4.1 Pipettenlösungen verschiedener Autoren im Vergleich ... 69 Tabelle 4.2 Badlösungen verschiedener Autoren im Vergleich ... 69

Liste der akademischen Lehrer

Meine akademischen Lehrer…

…in Marburg

Aumüller, Basler, Baum, Bien, Bischof, Boudriot, Braun, Breckle, Cruse, Eilers, Elsässer, Engelhaaf, Garten, Geger, Gerdes, Grundmann, Gudermann, Hamer, Hanley, Hasilik, Heeg, Heimann, Hermann-Lingen, Hertl, Jungclas, Kircher, Klenk, Kogel, Konrad, Krieg, Kroll, Kunz, Lang, Langer, Leube, Lill, Löffler, Lohoff, Maier, Mandrek, Martin, Mederos-Schnitzer, Moll, Müller, Mueller, Musset, Neuert, Oeffner, Oertel, Opitz, Plant, Rager, Renz, Riera, Röhm, Röper, Rosenow, Schäfer, Schimke, Schlotzhauer, Schmidt, Schneider, Schofer, Sommer, Schrader, Schu, Schulz, Stiller, Suske, Vogelmeier, Vogt, Voigt, Weihe, Weiler, Werner, Westermann, Wulf, Werner.

… in Bielefeld

Bartolomaeus, Dietz, Feldmann, Jockusch, Reißland, Ruppel, Tschirnhaus, Weber

… in Lippstadt Marke, Matz, Kogel

… in Palma de Mallorca/Spanien

Gessner, Hörstmann, Linnenbecker, Terasa

… in Alicante/Spanien

Candela Gomis, Compañ Rosique, Diez Miralles ... in Schwalmstadt

Frick, Hesselbarth, Puplat, Schulze, Weber