Nilius Bernd, Prenen Jean, Voets Thomas, Droogmans Guy
Laboratorium voor Fysiologie Campus Gasthuisberg, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
Pflugers Arch. 2004 Apr;448(1):70-5. doi: 10.1007/s00424-003-1221-x. Epub 2004 Jan 31.
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+), 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+), (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.
TRPM4b（与短剪接变体TRPM4a不同）是一种Ca(2+)激活但Ca(2+)不可渗透的阳离子通道。我们研究了内向外膜片中的TRPM4电流。在内侧施加超微摩尔浓度的Ca(2+)，即Ca(2+)，可激活TRPM4，其半最大有效浓度（EC(50)）值为0.37 mM，该值远高于全细胞电流的EC(50)值。当Ca(2+)高于1 mM时电流幅度下降（半数抑制浓度（IC(50)）为9.3 mM）。Sr(2+)可部分替代Ca(2+)，而Ba(2+)则不能。ATP、ADP、AMP和AMP-PNP均能快速且可逆地抑制TRPM4，其IC(50)值在2至19 μM之间（在+100 mV时）。腺苷在630 μM时也能阻断TRPM4。高ATP浓度下的阻断作用不完全，且不受游离Mg(2+)存在的影响。ADP诱导的阻断作用最敏感，IC(50)为2.2 μM。对于游离ATP(4-)对TRPM4的抑制作用，计算得出IC(50)值为1.7±0.3 μM。浓度高达1 mM的GTP、UTP和CTP不会诱导类似的阻断作用。精胺以61 μM的IC(50)阻断TRPM4电流。总之，TRPM4是一种可被细胞内核苷酸和多胺有效调节的通道。
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