Intracellular nucleotides and polyamines inhibit the Ca2+-activated cation channel TRPM4b. Export

@article{citeulike:1292092, abstract = {TRPM4b (in contrast to the short splice variant TRPM4a) is a Ca(2+)-activated but Ca(2+)-impermeable cation channel. We have studied TRPM4 currents in inside-out patches. Supramicromolar Ca(2+) concentrations applied at the inner side, [Ca(2+)](i), activated TRPM4 with an EC(50) value of 0.37 mM, a value that is much higher than that of whole-cell currents. Current amplitudes decreased above 1 mM [Ca(2+)](i), (IC(50) 9.3 mM). Sr(2+) but not Ba(2+)could partially substitute for Ca(2+). ATP, ADP, AMP and AMP-PNP all quickly and reversibly inhibited TRPM4 with IC(50) values between 2 and 19 microM (at +100 mV). Adenosine also blocked TRPM4 at 630 microM. The block at high ATP concentrations was incomplete and was not affected by the presence of free Mg(2+). ADP induced the most sensitive block with an IC(50) of 2.2 microM. For inhibition of TRPM4 by free ATP(4-), an IC(50) value of 1.7+/-0.3 microM was calculated. GTP, UTP and CTP at concentrations up to 1 mM did not induce a similar block. Spermine blocked TRPM4 currents with an IC(50) of 61 microM. In conclusion, TRPM4 is a channel that can be effectively modulated by intracellular nucleotides and polyamines.}, address = {Laboratorium voor Fysiologie Campus Gasthuisberg, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. bernd.nilius@med.kuleuven.ac.be}, author = {Nilius, B. and Prenen, J. and Voets, T. and Droogmans, G.}, citeulike-article-id = {1292092}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00424-003-1221-x}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/14758478}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=14758478}, doi = {10.1007/s00424-003-1221-x}, issn = {0031-6768}, journal = {Pflugers Arch}, keywords = {cation, channel, medsci733, non, selective, trpm4}, month = {April}, number = {1}, pages = {70--75}, posted-at = {2007-05-13 05:46:37}, priority = {2}, title = {Intracellular nucleotides and polyamines inhibit the Ca2+-activated cation channel TRPM4b.}, url = {http://dx.doi.org/10.1007/s00424-003-1221-x}, volume = {448}, year = {2004} }

TY - JOUR ID - citeulike:1292092 L3 - citeulike-article-id:1292092 N2 - TRPM4b (in contrast to the short splice variant TRPM4a) is a Ca(2+)-activated but Ca(2+)-impermeable cation channel. We have studied TRPM4 currents in inside-out patches. Supramicromolar Ca(2+) concentrations applied at the inner side, [Ca(2+)](i), activated TRPM4 with an EC(50) value of 0.37 mM, a value that is much higher than that of whole-cell currents. Current amplitudes decreased above 1 mM [Ca(2+)](i), (IC(50) 9.3 mM). Sr(2+) but not Ba(2+)could partially substitute for Ca(2+). ATP, ADP, AMP and AMP-PNP all quickly and reversibly inhibited TRPM4 with IC(50) values between 2 and 19 microM (at +100 mV). Adenosine also blocked TRPM4 at 630 microM. The block at high ATP concentrations was incomplete and was not affected by the presence of free Mg(2+). ADP induced the most sensitive block with an IC(50) of 2.2 microM. For inhibition of TRPM4 by free ATP(4-), an IC(50) value of 1.7+/-0.3 microM was calculated. GTP, UTP and CTP at concentrations up to 1 mM did not induce a similar block. Spermine blocked TRPM4 currents with an IC(50) of 61 microM. In conclusion, TRPM4 is a channel that can be effectively modulated by intracellular nucleotides and polyamines. IS - 1 JF - Pflugers Arch SN - 0031-6768 AD - Laboratorium voor Fysiologie Campus Gasthuisberg, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. bernd.nilius@med.kuleuven.ac.be EP - 75 TI - Intracellular nucleotides and polyamines inhibit the Ca2+-activated cation channel TRPM4b. VL - 448 SP - 70 KW - cation KW - channel KW - medsci733 KW - non KW - selective KW - trpm4 AU - Nilius, B AU - Prenen, J AU - Voets, T AU - Droogmans, G PY - 2004/04// UR - http://dx.doi.org/10.1007/s00424-003-1221-x ER -