Optical control of L-type Ca2+ channels using a diltiazem photoswitch

Timm Fehrentz; Florian M.E. Huber; Nina Hartrampf; Tobias Bruegmann; James A. Frank; Nicholas H.F. Fine; Daniela Malan; Johann G. Danzl; Denis B. Tikhonov; Martin Sumser; Philipp Sasse; David J. Hodson; Boris S. Zhorov; Nikolaj Klöcker; Dirk Trauner

doi:10.1038/s41589-018-0090-8

Optical control of L-type Ca²⁺ channels using a diltiazem photoswitch

Timm Fehrentz, Florian M.E. Huber, Nina Hartrampf, Tobias Bruegmann, James A. Frank, Nicholas H.F. Fine, Daniela Malan, Johann G. Danzl, Denis B. Tikhonov, Martin Sumser, Philipp Sasse, David J. Hodson, Boris S. Zhorov, Nikolaj Klöcker, Dirk Trauner

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29 Scopus citations

Abstract

L-type Ca²⁺ channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic β-cell function and cardiac activity under optical control.

Original language	English (US)
Pages (from-to)	764-767
Number of pages	4
Journal	Nature Chemical Biology
Volume	14
Issue number	8
DOIs	https://doi.org/10.1038/s41589-018-0090-8
State	Published - Aug 1 2018
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1038/s41589-018-0090-8

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Fehrentz, T., Huber, F. M. E., Hartrampf, N., Bruegmann, T., Frank, J. A., Fine, N. H. F., Malan, D., Danzl, J. G., Tikhonov, D. B., Sumser, M., Sasse, P., Hodson, D. J., Zhorov, B. S., Klöcker, N., & Trauner, D. (2018). Optical control of L-type Ca²⁺ channels using a diltiazem photoswitch. Nature Chemical Biology, 14(8), 764-767. https://doi.org/10.1038/s41589-018-0090-8

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title = "Optical control of L-type Ca2+ channels using a diltiazem photoswitch",

abstract = "L-type Ca2+ channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic β-cell function and cardiac activity under optical control.",

author = "Timm Fehrentz and Huber, {Florian M.E.} and Nina Hartrampf and Tobias Bruegmann and Frank, {James A.} and Fine, {Nicholas H.F.} and Daniela Malan and Danzl, {Johann G.} and Tikhonov, {Denis B.} and Martin Sumser and Philipp Sasse and Hodson, {David J.} and Zhorov, {Boris S.} and Nikolaj Kl{\"o}cker and Dirk Trauner",

note = "Funding Information: Forschungsgemeinschaft (DFG, German Research Foundation, GRK1873, SA 1785/7-1, SA 1785/9-1). Funding Information: We would like to thank G.R. Lewin and M. Moroni (MDC Berlin) for the TRAAK-GFP construct, M.B. Johnny (Johns Hopkins University) for Cav1.2Δ1671-G12-CaMMUTconstruct, J. Striessnig (University of Innsbruck) for Cav1.3, Cav1.2, β3, α2δ constructs and H. Abriel (University of Bern) for a HEK293 stable cell line expressing Nav1.5. T.F. and J.G.D thank S.W. Hell for general support. D.T. was supported by the Deutsche Forschungsgemeinschaft (SFB 749) and Center for Integrated Protein Science Munich (CIPSM). M.S. was supported by the DFG (SPP1926). N.K. was supported by the Deutsche Forschungsgemeinschaft (SFB 1116, TP A01) and the BMBF (DZHK, FKZ: 81 × 2800159). D.J.H. was supported by a Diabetes UK R.D. Lawrence (12/0004431) and EFSD/Novo Nordisk Rising Star Fellowships, a Wellcome Trust Institutional Support Award, and COMPARE Primer, MRC Project (MR/N00275X/1) and ERC Starting Grants (OptoBETA; 715884). N.H. thanks the “Deutsche Telekom Stiftung” and the LMUMentoring program for financial support. B.S.Z. acknowledges grants from NSERC, Canada (GRPIN-2014-04894) and Russian Science Foundation (17-15-01292). P.S. was supported by the Deutsche Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = aug,

day = "1",

doi = "10.1038/s41589-018-0090-8",

language = "English (US)",

volume = "14",

pages = "764--767",

journal = "Nature Chemical Biology",

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TY - JOUR

T1 - Optical control of L-type Ca2+ channels using a diltiazem photoswitch

AU - Fehrentz, Timm

AU - Huber, Florian M.E.

AU - Hartrampf, Nina

AU - Bruegmann, Tobias

AU - Frank, James A.

AU - Fine, Nicholas H.F.

AU - Malan, Daniela

AU - Danzl, Johann G.

AU - Tikhonov, Denis B.

AU - Sumser, Martin

AU - Sasse, Philipp

AU - Hodson, David J.

AU - Zhorov, Boris S.

AU - Klöcker, Nikolaj

AU - Trauner, Dirk

N1 - Funding Information: Forschungsgemeinschaft (DFG, German Research Foundation, GRK1873, SA 1785/7-1, SA 1785/9-1). Funding Information: We would like to thank G.R. Lewin and M. Moroni (MDC Berlin) for the TRAAK-GFP construct, M.B. Johnny (Johns Hopkins University) for Cav1.2Δ1671-G12-CaMMUTconstruct, J. Striessnig (University of Innsbruck) for Cav1.3, Cav1.2, β3, α2δ constructs and H. Abriel (University of Bern) for a HEK293 stable cell line expressing Nav1.5. T.F. and J.G.D thank S.W. Hell for general support. D.T. was supported by the Deutsche Forschungsgemeinschaft (SFB 749) and Center for Integrated Protein Science Munich (CIPSM). M.S. was supported by the DFG (SPP1926). N.K. was supported by the Deutsche Forschungsgemeinschaft (SFB 1116, TP A01) and the BMBF (DZHK, FKZ: 81 × 2800159). D.J.H. was supported by a Diabetes UK R.D. Lawrence (12/0004431) and EFSD/Novo Nordisk Rising Star Fellowships, a Wellcome Trust Institutional Support Award, and COMPARE Primer, MRC Project (MR/N00275X/1) and ERC Starting Grants (OptoBETA; 715884). N.H. thanks the “Deutsche Telekom Stiftung” and the LMUMentoring program for financial support. B.S.Z. acknowledges grants from NSERC, Canada (GRPIN-2014-04894) and Russian Science Foundation (17-15-01292). P.S. was supported by the Deutsche Publisher Copyright: © 2018 The Author(s).

PY - 2018/8/1

Y1 - 2018/8/1

N2 - L-type Ca2+ channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic β-cell function and cardiac activity under optical control.

AB - L-type Ca2+ channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic β-cell function and cardiac activity under optical control.

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AN - SCOPUS:85049952718

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SP - 764

EP - 767

JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 8

ER -

Optical control of L-type Ca²⁺ channels using a diltiazem photoswitch

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