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Glühbirne

rEstus, a fluorescent membrane voltage indicator

Foto: FSU Biophysik

Visualizing the electrical whispering of cells

Rühl, P., A.G. Nair, N. Gawande, S.N.C.W. Dehiwalage, L. Münster, R. Schönherr, S.H. Heinemann

An ultrasensitive fluorescent voltage indicator unvovers the electrical acivity of non-excitable cells

Advanced Science (2024) e2307938. PMID: 38526185

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SeMet-containing sodium channels

Illustration: FSU Biophysik

SeMet-containing sodium channels

Hussein, R.A., M. Ahmed, S.H. Heinemann

Selenomethionine mis-incorporation and redox-dependent voltage-gated sodium channel gain of function

Journal of Neurochemistry (2023) 167(2): 262-276. PMID: 36152916

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SeMet Incorporation

Illustration: FSU Biophysik

Optical sensing of SeMet incorporation

Hussein, R.A., M. Ahmed, N. Kuldyushev, R. Schönherr, S.H. Heinemann

Selenomethionine incorporation in proteins of individual mammalian cells detected with a genetically encoded fluorescent sensor

Free Radical Biology and Medicine (2022) 192: 191-199. PMID: 36152916

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Hemin inhibits cadiac NaV channels

Abbildung: FSU Biophysik

Extracellular hemin inhibits cardiac voltage-gated Na+ channels

Gessner, G., M. Jamili, P. Tomczyk, D. Menche, R. Schönherr, T. Hoshi, S.H. Heinemann

Hemin is a reverse use-dependent gating modifier of cardiac voltage-gated Na+ channels

Biological Chemistry (2022) 403: 1067-1081. PMID: 36038266

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Fluorescent Sensor for Methionine Oxidation

Illustration: FSU Biophysik

Optical monitoring of protein posttranslational modification

Kuldyushev, N., R. Schönherr, I. Coburger, M. Ahmed, R.A. Hussein, E. Wiesel, A. Godbole, T. Pfirrmann, T. Hoshi, S.H. Heinemann

A GFP-based ratiometric sensor for cellular methionine oxidation

Talanta (2022) 243:123332. PMID: 35276500

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Genetically Encoded Voltage Indicator

Illustration: FSU Biophysik

Optical tracking of membrane potential in cell cultures

Rühl, P., J. Langner, J. Reidel, T. Hoshi, R. Schönherr, S.H. Heinemann

Monitoring of compound resting membrane potential of cell cultures with ratiometric genetically encoded voltage indicators

Communications Biology (2021) 4:1164. PMID: 34620975

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Photoactivation of Dendra2 by NIR radiation of UCNPs

Illustration: FSU Biophysik

Photonic modulation with upconverting nanoparticles

Drees, C., P. Rühl,  J. Czerny, G. Chandra, J. Bajorath, M. Haase, S.H. Heinemann, J. Piehler

Diffraction-unlimited photomanipulation at the plasma membrane via specifically targeted upconversion nanoparticles

Nano Letters (2021) 21:8025-8034. PMID: 34519216

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CORM-S1 releases CO and Fe2+, both of which activate BK channels

Illustration: FSU Biophysik

Rapidly photoreleased Fe2+ activates BKCa channels

Gessner, G., P. Rühl, M. Westerhausen, T. Hoshi, S.H. Heinemann

Fe2+-mediated activation of BKCa channels by rapid photolysis of CORM-S1 releasing CO and Fe2+

ACS - Chemical Biology (2020) 15(8): 2098–2106. PMID: 32667185

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N-terminal sequence of Kv1.4 (top); current traces of Kv1.4 before and after polysulfide application (left); MALDI spectra showing sulfhydration of C13 in the N-terminal inactivation peptide.

Illustration: FSU Biophysik

Sulfhydration eliminates potassium channel inactivation

Yang, K., I. Coburger, J.M. Langner, N. Peter, T. Hoshi, R. Schönherr, S.H. Heinemann

Modulation of K+ channel N-type inactivation by sulfhydration through hydrogen sulfide and polysulfides

Pflügers Archiv European Journal of Physiology (2019) 471: 557-571. PMID: 32388729

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Dual effects of tricarbonyldichlororuthenium(II) dimer (CORM-2) on voltage-dependent potassium channels. Channel modification may result from binding of either carbon monoxide (blue) and/or of Ru(CO)2 fragments (red). The latter involves adduction to target histidines and, thus, can be quenched by excess free histidine or histidine-containing proteins such as human serum albumin.

Illustration: FSU Biophysik

CO-releasing molecules standing offside?

Gessner, G., N. Sahoo, S.M. Swain, G. Hirth, R. Schönherr, R. Mede, M. Westerhausen, H.H. Brewitz, P. Heimer, D. Imhof, T. Hoshi, S.H. Heinemann

CO-independent modification of K+ channels by tricarbonyldichloro-ruthenium(II) dimer (CORM-2).

European Journal of Pharmacology (2017) 815: 33-41

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Pulse protocol (top) and current recordings of roNaV2 channels in HEK293 cells (bottom). The blue bar marks illumination of the cell with blue light via a 63x objective. The red curve is a mono-exponential fit to describe the time course of inactivation loss upon illumination.

Illustration: FSU Biophysik

Sodium channel with selenocysteine senses phototoxicity

Ojha, N.K., E. Leipold, R. Schönherr, T. Hoshi, S.H. Heinemann

Non-photonic sensing of membrane-delimited reactive species with a Na+ channel protein containing selenocysteine.

Scientific Reports (2017) 7: 46003

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Blocking effects of 10 µM µ-SIIIA (blue) and µ-PIIIA (red) on ion currents of the indicated voltage-gated ion channels.

Illustration: FSU Biophysik

µ-Conotoxins block Kv channels

Leipold, E., F. Ullrich, M. Thiele, A.A. Tietze, H. Terlau, D. Imhof, S.H. Heinemann

Subtype-specific block of voltage-gated K+ channels by µ-conotoxins.

Biochemical and Biophysical Research Communications (2017) 482: 1135-1140

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Stimulated action potentials of DRG neurons before (black) and after 150 s illumination with blue light (blue) from wild-type (left) and NaV1.8-deficient mice (right).

Illustration: FSU Biophysik

Stress susceptibility of Nav1.8 channels in DRG neurons

Schink, M., E. Leipold, J. Schirmeyer, R. Schönherr, T. Hoshi, S.H. Heinemann

Reactive species modify Nav1.8 channels and affect action potentials in murine dorsal root ganglion neurons

Pflügers Archiv European Journal of Physiology (2016) 468: 99-110

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Score pattern for potential calmodulin binding to the N terminus of Kvβ1.1 (top) and current recordings of Kv1.1+Kvβ1.1 channels with and without Ca(2+)/CaM for wild-type Kvβ1.1 (left) and after replacement of three asparagine residues for arginine (right).

Illustration: FSU Biophysik

Fine-tuning of Kv channel inactivation by calcium

Swain, S.M., N. Sahoo, S. Dennhardt, R. Schönherr, S.H. Heinemann

Ca/calmodulin regulates Kvβ1.1-mediated inactivation of voltage-gated K+ channels.

Scientific Reports (2015) 5: 15509

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Representative current traces measured in the whole-cell mode in response to depolarizations ranging from -127 to 3 mV of HEK 293T cells expressing human NaV1.9 (left) or chimera NaV1.9-C4 (right).

Illustration: FSU Biophysik

Functional expression of Nav1.9 chimeras

Goral, R.O., E. Leipold, E. Nematian-Ardestani, S.H. Heinemann

Heterologous expression of Nav1.9 chimeras in various cell systems.

Pflügers Archiv European Journal of Physiology (2015) 467: 2423-2435

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Response of roGFP2 (top) and the ratiometric roNaV signal (bottom) to blue light. At -50 mV roNaV is inactivated and, thus, protected from ROS attack.

Illustration: FSU Biophysik

roNaV: A non-photonic gateable ROS sensor

Ojha, N.K., E. Nematian-Ardestani, S. Neugebauer, B. Borowski, A. El-Hussein, T. Hoshi, E. Leipold, S.H. Heinemann

Sodium channels as gateable non-photonic sensors for membrane-delimited reactive species.

Biochimica et Biophysica Acta - Biomembranes (2014) 1838: 1412-1419

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Kv1 4 current traces without (black) and with hemin (red). Part of the N-terminal ball domain with a docked hemin moiety.

Illustration: FSU Biophysik

Heme is a potent regulator of potassium channel inactivation

Sahoo, N., N. Goradia, O. Ohlenschläger, R. Schönherr, M. Friedrich, W. Plass, R. Kappl, T. Hoshi, S.H. Heinemann

Heme impairs the ball-and-chain inactivation of potassium channels.

Proceedings of the National Academy of Sciences USA Plus (2013) 110: E4036-4044

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A mutation in SCN11A causes a gain-of-function of the voltage-gated sodium channel NaV1.9 and leads to suppression of the electrical signaling in nociceptive neurons.

Illustration: FSU Biophysik

A mutation in SCN11A eliminates pain sensation

Leipold, E., L. Liebmann, G.C. Korenke, T. Heinrich, S. Gießelmann, J. Baets, M. Ebbinghaus, R.O. Goral, T. Stödberg, J.C. Hennings, M. Bergmann, J. Altmüller, H. Thiele, A. Wetzel, P. Nürnberg, V. Timmerman, P. de Jonghe, R. Blum, H.G. Schaible, J. Weis, S.H. Heinemann, C.A. Hübner, I. Kurth

A de novo gain-of-function mutation in SCN11A causes loss of pain perception.

Nature Genetics (2013) 45: 1399-1404

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Blood pressure recordings on anesthesized mice upon injection of DHA and DHA EE (experiments performed by Bianka Wissuwa).

Illustration: FSU Biophysik

Omega-3 fatty acids lower blood pressure

Hoshi, T., B. Wissuwa, Y. Tian, N. Tajima, R. Xu, M. Bauer, S.H. Heinemann, S. Hou

Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca2+-dependent K+ channels

Proceedings of the National Academy of Sciences USA (2013) 110: 4816-4821

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