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Research ArticleORIGINAL ARTICLE

Activation of the Melastatin-Related Cation Channel TRPM3 by d-erythro-Sphingosine

Christian Grimm, Robert Kraft, Günter Schultz and Christian Harteneck
Molecular Pharmacology March 2005, 67 (3) 798-805; DOI: https://doi.org/10.1124/mol.104.006734
Christian Grimm
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Robert Kraft
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Günter Schultz
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Christian Harteneck
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This article has a correction. Please see:

  • Correction to “Activation of the melastatin-related cation channel TRMP3 by d-erythro-sphingosine” - April 01, 2005

Abstract

TRPM3, a member of the melastatin-like transient receptor potential channel subfamily (TRPM), is predominantly expressed in human kidney and brain. TRPM3 mediates spontaneous Ca2+ entry and nonselective cation currents in transiently transfected human embryonic kidney 293 cells. Using measurements with the Ca2+-sensitive fluorescent dye fura-2 and the whole-cell patch-clamp technique, we found that d-erythro-sphingosine, a metabolite arising during the de novo synthesis of cellular sphingolipids, activated TRPM3. Other transient receptor potential (TRP) channels tested [classic or canonical TRP (TRPC3, TRPC4, TRPC5), vanilloid-like TRP (TRPV4, TRPV5, TRPV6), and melastatin-like TRP (TRPM2)] did not significantly respond to application of sphingosine. Sphingosine-induced TRPM3 activation was not mediated by inhibition of protein kinase C, depletion of intracellular Ca2+ stores, and intracellular conversion of sphingosine to sphingosine-1-phosphate. Although sphingosine-1-phosphate and ceramides had no effect, two structural analogs of sphingosine, dihydro-d-erythro-sphingosine and N,N-dimethyl-d-erythro-sphingosine, also activated TRPM3. Sphingolipids, including sphingosine, are known to have inhibitory effects on a variety of ion channels. Thus, TRPM3 is the first ion channel activated by sphingolipids.

  • Received August 30, 2004.
  • Accepted November 18, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 67 (3)
Molecular Pharmacology
Vol. 67, Issue 3
1 Mar 2005
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Research ArticleORIGINAL ARTICLE

Activation of the Melastatin-Related Cation Channel TRPM3 by d-erythro-Sphingosine

Christian Grimm, Robert Kraft, Günter Schultz and Christian Harteneck
Molecular Pharmacology March 1, 2005, 67 (3) 798-805; DOI: https://doi.org/10.1124/mol.104.006734

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Research ArticleORIGINAL ARTICLE

Activation of the Melastatin-Related Cation Channel TRPM3 by d-erythro-Sphingosine

Christian Grimm, Robert Kraft, Günter Schultz and Christian Harteneck
Molecular Pharmacology March 1, 2005, 67 (3) 798-805; DOI: https://doi.org/10.1124/mol.104.006734
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