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

• Published in: Nature chemical biology Vol. 14; no. 8; pp. 764 - 767
• Main Authors: Fehrentz, Timm, Huber, Florian M. E., Hartrampf, Nina, Bruegmann, Tobias, Frank, James A., Fine, Nicholas H. F., Malan, Daniela, Danzl, Johann G., Tikhonov, Denis B., Sumser, Martin, Sasse, Philipp, Hodson, David J., Zhorov, Boris S., Klöcker, Nikolaj, Trauner, Dirk
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-08-2018; Nature Publishing Group
• Subjects: 631/92/269; 639/638/92; 692/699/75; Antihypertensives; Arrhythmia; Beta cells; Biochemical Engineering; Biochemistry; Biology; Bioorganic Chemistry; Brief Communication; Calcium channels; Calcium channels (L-type); Calcium influx; Calcium ions; Cell Biology; Channels; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Contraction; Diltiazem; Endocrinology; Heart rate; Hormones; Insulin; Metabolism; Optical control; Pancreas; Physiology
• ISSN: 1552-4450; 1552-4469
• DOI: 10.1038/s41589-018-0090-8

L-type Ca
2+
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.
A photoswitchable probe to control Ca
2+
influx through L-type Ca
2+
channels is useful in pancreatic β cells and can be employed to modulate beating rate in explanted hearts.