TRAM-34 inhibits nonselective cation channels.
TRAM-34 has been demonstrated to inhibit intermediate-conductance Ca(2+)-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 Ca(2+) concentration of microglial cells were effectively reduced in the presence of TRAM-34. At a concentration of 1 microM, TRAM-34 inhibited LPC-induced Ca(2+) signals by 60%. The TRAM-34-induced reduction of LPC-induced Ca(2+) increases cannot be related to the inhibition of Ca(2+)-activated K(+) channels. In contrast to TRAM-34, the Ca(2+)-activated K(+) channel inhibitor charybdotoxin did not affect LPC-induced increases in the intracellular Ca(2+) 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 Ca(2+)-activated K(+) channels.
Schilling
Tom
T
Institute of Physiology, Medical Faculty Charité, Tucholskystrasse 2, 10117 Berlin, Germany.
Eder
Claudia
C
D000818:Animals; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D018999:Charybdotoxin / Q000494:pharmacology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000502:physiology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors* / Q000187:drug effects* / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology*
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496925:Kcnn4 protein, mouse; D008244:Lysophosphatidylcholines; D009498:Neurotoxins; D024681:Potassium Channels, Calcium-Activated; D011720:Pyrazoles; C411671:TRAM 34; D018999:Charybdotoxin; D002118:Calcium