TRP Genes
Candidates for Nonselective Cation Channels and Store-Operated Channels in Insulin-Secreting Cells
- 1Department of Neurobiology, Physiology, and Pharmacology, the University of Chicago, Chicago, Illinois
- 2Department of Medicine and Committee in Cell Physiology, the University of Chicago, Chicago, Illinois
Abstract
Nonselective cation channels may play a role in insulin secretion by regulating pancreatic β-cell plasma membrane potential, Ca2+ homeostasis, and thereby glucose signaling. Transient receptor potential channel (TRPC)-related genes encode nonselective cation channels, some of which are similar to those described for β-cells. Some TRPC-like channels are activated via G-protein–coupled mechanisms, some have been reported to be calcium-store–operated channels (SOC), and others are activated by novel signaling molecules or are sensitive to pressure and osmotic strength. Here we report the cloning and expression of mSTRPC4 from a mouse insulinoma cDNA library. mSTRPC4 encoded a protein of 97 kd, expressed in both endocrine cells and the brain. Stable cell lines expressing mSTRPC4 showed abundant mSTRPC4 protein, but no reproducible currents could be detected. mSTRPC4 therefore probably functions as a heteromultimer. We also report that LTRPC2, a G-protein and adenosine 5′-diphosphoribose (ADPR)-activated nonselective cation channel, is also expressed in human islets. TRPC-like channels may provide a pathway for depolarization or Ca2+ entry in β-cells and may be interesting targets for manipulating β-cell function.
Footnotes
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Address correspondence and reprint requests to l-philipson{at}uchicago.edu.
Accepted for publication 15 June 2001.
ADPR, adenosine 5′-diphosphoribose; cADPR, cyclic adenosine 5′-diphosphoribose; CCE, capacitative calcium entry; DMEM, Dulbecco’s modified Eagle’s medium; EYFP, enhanced yellow fluorescence protein; FBS, fetal bovine serum; ICRAN, calcium-release activated nonselective cation current; IP3, inositol 1,4,5-trisphosphate; RACE, receptor-activated calcium entry; RT-PCR, reverse transcriptase–polymerase chain reaction; SOC, store-operated channel; SSC, standard saline citrate; TRPC, transient receptor potential channel.
The symposium and the publication of this article have been made possible by an unrestricted educational grant from Servier, Paris.
