TY  - JOUR
A1  - Moll, Heidrun
A1  - Müller, Christoph
A1  - Gillitzer, Reinhard
A1  - Fuchs, Harald
A1  - Röllinghoff, Martin
A1  - Simon, Markus M.
A1  - Kramer, Michael D.
T1  - Expression of T-cell-associated serine proteinase-1 during murine Leishmania major infection correlates with susceptibility to disease
N2  - The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis.
KW  - Biologie
KW  - Immunologie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61311
ER  - 
TY  - JOUR
A1  - vom Dahl, Christian
A1  - Müller, Christoph Emanuel
A1  - Berisha, Xhevat
A1  - Nagel, Georg
A1  - Zimmer, Thomas
T1  - Coupling the cardiac voltage-gated sodium channel to channelrhodopsin-2 generates novel optical switches for action potential studies
JF  - Membranes
N2  - Voltage-gated sodium (Na\(^+\)) channels respond to short membrane depolarization with conformational changes leading to pore opening, Na\(^+\) influx, and action potential (AP) upstroke. In the present study, we coupled channelrhodopsin-2 (ChR2), the key ion channel in optogenetics, directly to the cardiac voltage-gated Na\(^+\) channel (Na\(_v\)1.5). Fusion constructs were expressed in Xenopus laevis oocytes, and electrophysiological recordings were performed by the two-microelectrode technique. Heteromeric channels retained both typical Na\(_v\)1.5 kinetics and light-sensitive ChR2 properties. Switching to the current-clamp mode and applying short blue-light pulses resulted either in subthreshold depolarization or in a rapid change of membrane polarity typically seen in APs of excitable cells. To study the effect of individual K\(^+\) channels on the AP shape, we co-expressed either K\(_v\)1.2 or hERG with one of the Na\(_v\)1.5-ChR2 fusions. As expected, both delayed rectifier K\(^+\) channels shortened AP duration significantly. K\(_v\)1.2 currents remarkably accelerated initial repolarization, whereas hERG channel activity efficiently restored the resting membrane potential. Finally, we investigated the effect of the LQT3 deletion mutant ΔKPQ on the AP shape and noticed an extremely prolonged AP duration that was directly correlated to the size of the non-inactivating Na\(^+\) current fraction. In conclusion, coupling of ChR2 to a voltage-gated Na\(^+\) channel generates optical switches that are useful for studying the effect of individual ion channels on the AP shape. Moreover, our novel optogenetic approach provides the potential for an application in pharmacology and optogenetic tissue-engineering.
KW  - optogenetics
KW  - channelrhodopsin
KW  - voltage-gated Na\(^+\) channel
KW  - action potential
KW  - delayed rectifier potassium channel
KW  - hERG
KW  - long QT syndrome
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-288228
SN  - 2077-0375
VL  - 12
IS  - 10
ER  -