当细胞体积出现大的变化时，这对健康是不利的。因此，我们的细胞都配备有能保持其体积不变的机制。当周围环境渗透压发生变化，能改变细胞体积时，细胞会检测环境发生的变化，细胞会调整其内部的水分含量以应对这些影响。这是通过专门的离子通道（离子运动）将水分排出或吸收进入细胞体内来实现的。
然而，是什么分子负责导致这一现象发生仍是未知的。生理科学研究所、国家自然科学研究院副主席Yasunobu OKADA教授和他的研究小组已发现，能防止细胞因高渗条件而萎缩柄最终死亡（凋亡）的关键分子
渗透压异常升高可能是由于如剧烈运动或盐过多脱水等引起的。他们所描述的分子是TRPM2的变种包含截断的C端。TRPM2是色氨酸家族成员之一，是与疼痛、温度、压力、味觉和视觉等感觉改变相关的离子通道。
进一步研究发现TRPM2ΔC分子通过与CD38（循环ADP-核糖水解酶）结合而激活，CD38与II型糖尿病、癌症、艾滋病病毒感染者和催产素的分泌等有关。
Yasunobu OKADA教授希望研究针对新发现的分子开展的研究为研究疾病打开了方便之门，不仅有利于阐明疾病病理特点，而且在未来还可能开发出潜在治疗方法。（生物谷：Bioon）
doi:10.1113/jphysiol.2011.220947
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The ΔC splice-variant of TRPM2 is the hypertonicity-induced cation channel in HeLa cells, and the ecto-enzyme CD38 mediates its activation
Tomohiro Numata1,2,Kaori Sato1,Jens Christmann3,Romy Marx3,Yasuo Mori2,Yasunobu Okada1 andFrank Wehner1,3
Hypertonicity-induced cation channels (HICCs) are key-players in proliferation and apoptosis but their molecular correlate remains obscure. Furthermore, the activation profile of HICCs is not well defined yet. We report here that, in HeLa cells, intracellular adenosine diphosphate ribose (ADPr) and cyclic ADPr (cADPr), as supposed activators of TRPM2, elicited cation currents that were virtually identical to the osmotic activation of HICCs. Silencing of the expression of TRPM2 and of the ecto-enzyme CD38 (as a likely source of ADPr and cADPr) inhibited HICC as well as nucleotide-induced currents and, in parallel, the hypertonic volume response of cells (the regulatory volume increase, RVI) was attenuated. Quantification of intracellular cADPr levels and the systematic application of extra- vs. intracellular nucleotides indicate that the outwardly directed gradient rather than the cellular activity of ADPr and cADPr triggers TRPM2 activation, probably along with a simultaneous biotransformation of nucleotides. Cloning of TRPM2 identified the ΔC-splice variant as the molecular correlate of the HICC, which could be strongly supported by a direct comparison of the respective Ca2+ selectivity. Finally, immunoprecipitation and high-resolution FRET/FLIM imaging revealed the interaction of TRPM2 and CD38 in the native as well as in a heterologous (HEK293T) expression system. We propose transport-related nucleotide export via CD38 as a novel mechanism of TRPM2/HICC activation. With the biotransformation of nucleotides running in parallel, continuous zero trans-conditions are achieved which will render the system infinitely sensitive.
