Activation of heterologously expressed Drosophila TRPL channels: Ca2+ is not required and InsP3 is not sufficient.

Light-sensitive channels encoded by the Drosophila transient receptor potential-like gene (trpl) are activated in situ by an unknown mechanism requiring activation of Gq and phospholipase C (PLC). Recent studies have variously concluded that heterologously expressed TRPL channels are activated by direct Gq-protein interaction, InsP3 or Ca2+. In an attempt to resolve this confusion we have explored the mechanism of activation of TRPL channels co-expressed with a PLC-specific muscarinic receptor in a Drosophila cell line (S2 cells). Simultaneous whole-cell recordings and ratiometric Indo-1 Ca2+ measurements indicated that agonist (CCh)-induced activation of TRPL channels was not always associated with a rise in Ca2+. Internal perfusion with BAPTA (10 mM) reduced, but did not block, the response to agonist. In most cases, releasing caged Ca2+ facilitated the level of spontaneous channel activity, but similar concentrations (200-500 nM) could also inhibit TRPL activity. Releasing caged InsP3 invariably released Ca2+ from internal stores but had only a minor influence on TRPL activity and none at all when Ca2+ release was buffered with BAPTA. Caged InsP3 also failed to activate any light-sensitive channels in situ in Drosophila photoreceptors. Two phospholipase C inhibitors (U-73122 4 microM and bromo-phenacyl bromide 50 microM) reduced both spontaneous and agonist-induced TRPL activity in S2 cells. The results suggest that, as in situ, TRPL activation involves G-protein and PLC; that Ca2+ can both facilitate and in some cases inhibit TRPL channels, but that neither Ca2+ nor InsP3 is the primary activator of the channel.
AuthorsR C Hardie, P Raghu
JournalCell calcium (Cell Calcium) Vol. 24 Issue 3 Pg. 153-63 (Sep 1998) ISSN: 0143-4160 [Print] SCOTLAND
PMID9883270 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Calmodulin-Binding Proteins
  • Chelating Agents
  • Drosophila Proteins
  • Enzyme Inhibitors
  • Membrane Proteins
  • Recombinant Proteins
  • Transient Receptor Potential Channels
  • trpl protein, Drosophila
  • Egtazic Acid
  • Inositol 1,4,5-Trisphosphate
  • Carbachol
  • Type C Phospholipases
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium
  • Animals
  • Calcium (metabolism)
  • Calcium Signaling
  • Calmodulin-Binding Proteins (drug effects, genetics, metabolism)
  • Carbachol (pharmacology)
  • Chelating Agents (pharmacology)
  • Drosophila (genetics)
  • Drosophila Proteins
  • Egtazic Acid (analogs & derivatives, pharmacology)
  • Electrophysiology
  • Enzyme Inhibitors (pharmacology)
  • Inositol 1,4,5-Trisphosphate (metabolism)
  • Membrane Proteins (drug effects, genetics, metabolism)
  • Recombinant Proteins (genetics, metabolism)
  • Transient Receptor Potential Channels
  • Type C Phospholipases (antagonists & inhibitors, metabolism)

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