Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Tiapko, O; Bacsa, B; de la Cruz, GG; Glasnov, T; Groschner, K.
Optopharmacological control of TRPC channels by coumarin-caged lipids is associated with a phototoxic membrane effect.
Sci China Life Sci. 2016; 59(8):802-810 Doi: 10.1007/s11427-016-5095-5 [OPEN ACCESS]
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Leading authors Med Uni Graz

Bacsa Bernadett

Groschner Klaus

Tiapko Oleksandra

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Abstract:

Photouncaging of second messengers has been successfully employed to gain mechanistic insight of cellular signaling pathways. One of the most enigmatic processes of ion channel regulation is lipid recognition and lipid-gating of TRPC channels, which represents pivotal mechanisms of cellular Ca(2+) homeostasis. Recently, optopharmacological tools including caged lipid mediators became available, enabling an unprecedented level of temporal and spatial control of the activating lipid species within a cellular environment. Here we tested a commonly used caged ligand approach for suitability to investigate TRPC signaling at the level of membrane conductance and cellular Ca(2+) handling. We report a specific photouncaging artifact that is triggered by the cage structure coumarin at UV illumination. Electrophysiological characterization identified a light-dependent membrane effect of coumarin. UV light (340 nm) as used for photouncaging, initiated a membrane conductance specifically in the presence of coumarin as low as 30 μmol L(-1) concentrations. This conductance masked the TRPC3 conductance evoked by photouncaging, while TRPC-mediated cellular Ca(2+) responses were largely preserved. The observed light-induced membrane effects of the released caging moiety may well interfere with certain cellular functions, and prompt caution in using coumarin-caged second messengers in cellular studies.

Find related publications in this database (using NLM MeSH Indexing)

Calcium - metabolism

Calcium Channel Blockers - pharmacology

Calcium Signaling - drug effects

Calcium Signaling - radiation effects

Coumarins - chemistry

Diglycerides - chemistry

Diglycerides - pharmacology

HEK293 Cells -

Humans -

Imidazoles - pharmacology

Lipids - chemistry

Lipids - pharmacology

Luminescent Proteins - genetics

Luminescent Proteins - metabolism

Membrane Potentials - drug effects

Membrane Potentials - radiation effects

Microscopy, Fluorescence -

Patch-Clamp Techniques -

Photolysis - radiation effects

Signal Transduction - drug effects

Signal Transduction - radiation effects

TRPC Cation Channels - genetics

TRPC Cation Channels - metabolism

Ultraviolet Rays -

Find related publications in this database (Keywords)

caged diacylglycerols

TRPC channels

Ca2+ signaling

optopharmacology

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