Yu Jing, Park Mi-Hyeong, Choi Se-Young, Jo Su-Hyun
Department of Physiology, Institute of Bioscience and Biotechnology, BK21 plus Graduate Program, Kangwon National University College of Medicine, Hyoja-Dong, Chuncheon, 200-701, Republic of Korea.
Naunyn Schmiedebergs Arch Pharmacol. 2015 Jun;388(6):653-61. doi: 10.1007/s00210-015-1109-2. Epub 2015 Mar 7.
Glucocorticoids are hormones released in response to stress that are involved in various physiological processes including immune functions. One immune-modulating mechanism is achieved by the Kv1.3 voltage-dependent potassium channel, which is expressed highly in lymphocytes including effector memory T lymphocytes (TEM). Although glucocorticoids are known to inhibit Kv1.3 function, the detailed inhibitory mechanism is not yet fully understood. Here we studied the rapid non-genomic effects of cortisone and hydrocortisone on the human Kv1.3 channel expressed in Xenopus oocytes. Both cortisone and hydrocortisone reduced the amplitude of the Kv1.3 channel current in a concentration-dependent manner. Both cortisone and hydrocortisone rapidly and irreversibly inhibited Kv1.3 currents, eliminating the possibility of genomic regulation. Inhibition rate was stable relative to the degree of depolarization. Kinetically, cortisone altered the activating gate of Kv1.3 and hydrocortisone interacted with this channel in an open state. These results suggest that cortisone and hydrocortisone inhibit Kv1.3 currents via a non-genomic mechanism, providing a mechanism for the immunosuppressive effects of glucocorticoids.
糖皮质激素是机体在应激状态下释放的激素，参与包括免疫功能在内的多种生理过程。一种免疫调节机制是通过Kv1.3电压依赖性钾通道实现的，该通道在包括效应记忆T淋巴细胞（TEM）在内的淋巴细胞中高度表达。虽然已知糖皮质激素会抑制Kv1.3的功能，但其详细的抑制机制尚未完全阐明。在此，我们研究了可的松和氢化可的松对非洲爪蟾卵母细胞中表达的人类Kv1.3通道的快速非基因组效应。可的松和氢化可的松均以浓度依赖性方式降低Kv1.3通道电流的幅度。可的松和氢化可的松均能快速且不可逆地抑制Kv1.3电流，排除了基因组调控的可能性。抑制率相对于去极化程度是稳定的。从动力学角度来看，可的松改变了Kv1.3的激活门，而氢化可的松则在通道处于开放状态时与其相互作用。这些结果表明，可的松和氢化可的松通过非基因组机制抑制Kv1.3电流，为糖皮质激素的免疫抑制作用提供了一种机制。
