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

Nat Chem Biol. 2018 Aug;14(8):764-767. doi: 10.1038/s41589-018-0090-8. Epub 2018 Jul 16.

Authors

Timm Fehrentz^#¹, Florian M E Huber^#^{2

3}, Nina Hartrampf², Tobias Bruegmann^{4

5}, James A Frank^{2

6}, Nicholas H F Fine^{7

8}, Daniela Malan⁴, Johann G Danzl^{9

10}, Denis B Tikhonov¹¹, Martin Sumser², Philipp Sasse⁴, David J Hodson^{7

8}, Boris S Zhorov^{11

12

13}, Nikolaj Klöcker¹⁴, Dirk Trauner^{15

16}

Affiliations

¹ Institute of Neural and Sensory Physiology, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany. timm.fehrentz@gmail.com.
² Department of Chemistry, University of Munich and Center for Integrated Protein Science (CIPSM), Munich, Germany.
³ Roche Diagnostics GmbH, DXRERA, Penzberg, Germany.
⁴ Institute of Physiology I, Medical Faculty, University of Bonn, Bonn, Germany.
⁵ Research Training Group 1873, University of Bonn, Bonn, Germany.
⁶ Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁷ Institute of Metabolism and Systems Research (IMSR) and Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, UK.
⁸ Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.
⁹ Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
¹⁰ Institute of Science and Technology Austria, Klosterneuburg, Austria.
¹¹ Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
¹² Institute of Molecular Biology and Genetics, Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, Russia.
¹³ Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, Canada.
¹⁴ Institute of Neural and Sensory Physiology, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany. nikolaj.klocker@uni-duesseldorf.de.
¹⁵ Department of Chemistry, University of Munich and Center for Integrated Protein Science (CIPSM), Munich, Germany. dirktrauner@nyu.edu.
¹⁶ Department of Chemistry and Neuroscience Institute, New York University, New York, NY, USA. dirktrauner@nyu.edu.

^# Contributed equally.

PMID: 30013061
DOI: 10.1038/s41589-018-0090-8

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Calcium Channels, L-Type / chemistry
Calcium Channels, L-Type / metabolism*
Diltiazem / chemistry
Diltiazem / pharmacology*
Fluorescent Dyes / chemistry
Fluorescent Dyes / pharmacology*
Heart / drug effects*
Humans
Insulin-Secreting Cells / drug effects*
Insulin-Secreting Cells / metabolism
Light
Optical Imaging*
Photochemical Processes

Substances

Calcium Channels, L-Type
Fluorescent Dyes
Diltiazem

Grants and funding

MR/N00275X/1/MRC_/Medical Research Council/United Kingdom