Division of Nephrology, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States of America; Department of Medicine, Harvard Medical School, Boston, MA 02115, United States of America.
Quest Diagnostics, Inc., Seacaucus, NJ 07094, United States of America.
Blood Cells Mol Dis. 2021 Dec;92:102619. doi: 10.1016/j.bcmd.2021.102619. Epub 2021 Oct 29.
The molecular identity of Psickle, the deoxygenation-activated cation conductance of the human sickle erythrocyte, remains unknown. We observed in human sickle red cells that inhibitors of TRPA1 and TRPV1 inhibited Psickle, whereas a TRPV1 agonist activated a Psickle-like cation current. These observations prompted us to test the roles of TRPV1 and TRPA1 in Psickle in red cells of the SAD mouse model of sickle cell disease. We generated SAD mice genetically deficient in either TRPV1 or TRPA1. SAD;Trpv1 and SAD;Trpa1 mice were indistinguishable in appearance, hematological indices, and osmotic fragility from SAD mice. We found that deoxygenation-activated cation currents remained robust in SAD;Trpa1 and SAD;Trpv1 mice. In addition, Ca influx into SAD mouse red cells during prolonged deoxygenation was not reduced in red cells from SAD;Trpa1 and SAD;Trpv1 mice. We conclude that the nonspecific cation channels TRPA1 and TRPV1 are not required for deoxygenation to stimulate Psickle-like activity in red cells of the SAD mouse model of sickle cell disease. (159).
人镰状红细胞去氧激活阳离子电导 Psickle 的分子特征尚不清楚。我们在人镰状红细胞中观察到，TRPA1 和 TRPV1 的抑制剂可抑制 Psickle，而 TRPV1 激动剂则可激活类似于 Psickle 的阳离子电流。这些观察结果促使我们在镰状细胞病 SAD 小鼠模型的红细胞中测试 TRPV1 和 TRPA1 在 Psickle 中的作用。我们生成了基因敲除 TRPV1 或 TRPA1 的 SAD 小鼠。SAD;Trpv1 和 SAD;Trpa1 小鼠在外观、血液学指标和渗透脆性方面与 SAD 小鼠无明显差异。我们发现，去氧激活的阳离子电流在 SAD;Trpa1 和 SAD;Trpv1 小鼠中仍然很强。此外，在 SAD 小鼠红细胞中长时间去氧时，Ca2+内流并未减少 SAD;Trpa1 和 SAD;Trpv1 小鼠的红细胞。我们的结论是，非特异性阳离子通道 TRPA1 和 TRPV1 对于去氧刺激镰状细胞病 SAD 小鼠模型红细胞中类似于 Psickle 的活性不是必需的。(159)。
