期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2004
卷号:101
期号:43
页码:15535-15540
DOI:10.1073/pnas.0402081101
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Voltage-gated Kv1.1/Kv{beta}1.1 A-type channels, as a natural complex, can switch from fast to slow inactivation under oxidation/reduction conditions. The mode-switching of inactivation, which is mediated by a cysteine residue in the inactivation ball domain of the Kv{beta}1.1 N terminus, can regulate membrane electrical excitability. In the present study, we identified a mechanism whereby inactivation in Kv1.1/Kv{beta}1.1 channels is regulated by calcium influx. The rise in intracellular calcium, due to either influx from extracellular space or release from intracellular stores, eliminates fast inactivation induced by Kv{beta}1.1, resulting in slower inactivation and increased steady-state current. This oxidation-independent calcium effect is mediated through the Kv{beta}1.1 N terminus, not the C terminus. We propose that a coupling between calcium influx and inactivation of voltage-gated A-type K+ channels occurs as a result of membrane depolarization and may contribute to afterhyperpolarization as negative feedback to control neuronal excitability.