de Weille J R, Bassilana F, Lazdunski M, Waldmann R
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, Valbonne, France.
FEBS Lett. 1998 Aug 21;433(3):257-60. doi: 10.1016/s0014-5793(98)00916-8.
Non-inactivating or slowly inactivating proton-gated cation channels are thought to play an important role in the perception of pain that accompanies tissue acidosis. We have identified a novel human proton-gated cation channel subunit that has biphasic desensitisation kinetics with both a rapidly inactivating Na+-selective and a sustained component. The protein shares 84% sequence identity with the proton-gated cation channel rASIC3 (rDRASIC) from rat sensory neurones. The biphasic desensitisation kinetics and the sequence homology suggest that this novel clone (hASIC3) is the human orthologue of rASIC3 (rDRASIC). While rASIC3 (rDRASIC) requires very acidic pH (pH < 4.5) for activation of the sustained current, the non-inactivating hASIC3 current starts to be activated when the pH decreases to below pH 6. hASIC3 is an acid sensor and might play an important role in the detection of lasting pH changes in human. We localised the hASIC3 gene to the human chromosome 7q35, 6.4 cRad telomeric from the microsatellite AFMA082XC9.
非失活或缓慢失活的质子门控阳离子通道被认为在伴随组织酸中毒的疼痛感知中起重要作用。我们鉴定出一种新型人类质子门控阳离子通道亚基，其具有双相脱敏动力学，兼具快速失活的钠选择性成分和持续成分。该蛋白与大鼠感觉神经元的质子门控阳离子通道rASIC3（rDRASIC）具有84%的序列同一性。双相脱敏动力学和序列同源性表明，这个新克隆（hASIC3）是rASIC3（rDRASIC）的人类同源物。虽然rASIC3（rDRASIC）激活持续电流需要非常酸性的pH值（pH < 4.5），但当pH值降至6以下时，非失活的hASIC3电流开始被激活。hASIC3是一种酸传感器，可能在检测人类持续的pH值变化中起重要作用。我们将hASIC3基因定位到人类染色体7q35，距微卫星AFMA082XC9端粒6.4 cRad处。
