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Title: Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic beta cells
Authors: Wagner, Thomas F J ×
Loch, Sabine
Lambert, Sachar
Straub, Isabelle
Mannebach, Stefanie
Mathar, Ilka
Düfer, Martina
Lis, Annette
Flockerzi, Veit
Philipp, Stephan E
Oberwinkler, Johannes #
Issue Date: Dec-2008
Publisher: Macmillan Magazines Ltd.
Series Title: Nature Cell Biology vol:10 issue:12 pages:1421-30
Abstract: Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized to have rapid effects on membrane surface receptors that often have not been identified at the molecular level. We show here that TRPM3, a divalent-permeable cation channel, is rapidly and reversibly activated by extracellular pregnenolone sulphate, a neuroactive steroid. We show that pregnenolone sulphate activates endogenous TRPM3 channels in insulin-producing beta cells. Application of pregnenolone sulphate led to a rapid calcium influx and enhanced insulin secretion from pancreatic islets. Our results establish that TRPM3 is an essential component of an ionotropic steroid receptor enabling unanticipated crosstalk between steroidal and insulin-signalling endocrine systems.
URI: 
ISSN: 1465-7392
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Ion Channel Research
× corresponding author
# (joint) last author

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