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- Title
TRAM-34 inhibits nonselective cation channels.
- Authors
Schilling, Tom; Eder, Claudia
- Abstract
TRAM-34 has been demonstrated to inhibit intermediate-conductance Ca2+-activated K+ channels in a wide variety of cell types, including immune cells. In the present study, we investigated effects of TRAM-34 on microglial cells stimulated with lysophosphatidylcholine (LPC). LPC-induced increases in the intracellular Ca2+ concentration of microglial cells were effectively reduced in the presence of TRAM-34. At a concentration of 1 μM, TRAM-34 inhibited LPC-induced Ca2+ signals by 60%. The TRAM-34-induced reduction of LPC-induced Ca2+ increases cannot be related to the inhibition of Ca2+-activated K+ channels. In contrast to TRAM-34, the Ca2+-activated K+ channel inhibitor charybdotoxin did not affect LPC-induced increases in the intracellular Ca2+ concentration of microglial cells. Patch clamp experiments revealed a direct inhibitory effect of TRAM-34 on nonselective cation channels. Half-maximal inhibition of LPC-induced nonselective cation currents was determined at 38 nM TRAM-34. These data indicate that TRAM-34 may cause additional effects on immune cells that are unrelated to the well-described inhibition of Ca2+-activated K+ channels.
- Subjects
IMMUNITY; CELLS; CATIONS; NEUROGLIA; LYSOLECITHIN; CALCIUM; POTASSIUM
- Publication
Pflügers Archiv: European Journal of Physiology, 2007, Vol 454, Issue 4, p559
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-007-0232-4