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.
