Regulation of heterologously expressed transient receptor potential- like channels by calcium ions

Alexander Obukhov, G. Schultz, A. Lückhoff

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The Drosophila melanogaster gene product TRPL (transient receptor potential-like) is a Ca2+-permeable cation channel that contributes to the light-induced Ca2+ entry in Drosophila photoreceptors and bears homology to several recently cloned mammalian channels. Intracellular Ca2+ has been implicated to stimulate TRPL channels. This constitutes a potentially dangerous mechanism that may lead to Ca2+ overload. Therefore, we studied whether TRPL channels, like other Ca2+-permeable channels, are inhibited by intracellular Ca2+ concentrations in the micromolar range and whether this effect is mediated by calmodulin. In Sf9 cells expressing the TRPL gene along with histamine H1 receptors after infection with baculoviruses containing the corresponding complementary DNA, histamine-induced TRPL currents were inhibited by intracellular Ca2+ with an IC50 of 2.3 μM. Moreover, TRPL currents were reversibly attenuated by a preceding hyperpolarization. This attenuation reflected the action of an increased Ca2+ influx, since it was abolished in the absence of extracellular Ca2+ and enhanced by raising extracellular Ca2+ to 20 mM. Finally, the activity of TRPL channels in inside-out patches was reversibly inhibited by raising the Ca2+ concentration on the cytosolic side of the patches to 10-50 μM. Addition of calmodulin or the calmodulin inhibitor calmidazolium did not modify the inhibition of the TRPL by Ca2+. We conclude that high intracellular Ca2+ concentrations inhibit the TRPL, but no evidence was found for the requirement of calmodulin. This mechanism makes Ca2+ influx through the TRPL self-limiting. Furthermore, the TRPL may allow one to study the structural requirements for channel regulation by Ca2+.

Original languageEnglish (US)
Pages (from-to)487-495
Number of pages9
JournalNeuroscience
Volume85
Issue number2
DOIs
StatePublished - Apr 8 1998
Externally publishedYes

Fingerprint

Transient Receptor Potential Channels
Calmodulin
Ions
Calcium
calmidazolium
Sf9 Cells
Histamine H1 Receptors
Baculoviridae
Drosophila melanogaster
Histamine
Genes
Inhibitory Concentration 50
Drosophila
Cations
Complementary DNA
Light
Infection

Keywords

  • Calcium entry
  • Calcium regulation
  • Cation channels
  • Drosophila photoreceptors
  • Sf9 cells
  • TRPL

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Regulation of heterologously expressed transient receptor potential- like channels by calcium ions. / Obukhov, Alexander; Schultz, G.; Lückhoff, A.

In: Neuroscience, Vol. 85, No. 2, 08.04.1998, p. 487-495.

Research output: Contribution to journalArticle

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