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：2002
卷号：99
期号：22
页码：14494-14499
DOI：10.1073/pnas.222379999
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Substance P (SP) excites large neurons of the nucleus basalis (NB) by inhibiting an inward rectifier K+ channel (Kir). The properties of the Kir in NB (KirNB) in comparison with the G protein-coupled Kir (GIRK) were investigated. Single-channel recordings with the cell-attached mode showed constitutively active KirNB channels, which were inhibited by SP. When the recording method was changed from the on-cell to the inside-out mode, the channel activity of KirNB remained intact with its constitutive activity unaltered. Application of G{beta}1{gamma}2 to inside-out patches induced activity of a second type of Kir (GIRK). Application of G{beta}1{gamma}2, however, did not change the KirNB activity. Sequestering G{beta}1{gamma}2 with Gi2 abolished the GIRK activity, whereas the KirNB activity was not affected. The mean open time of KirNB channels (1.1 ms) was almost the same as that of GIRKs. The unitary conductance of KirNB was 23 pS (155 mM [K+]o), whereas that of the GIRK was larger (32-39 pS). The results indicate that KirNB is different from GIRKs and from any of the classical Kirs (IRKs). Whole-cell current recordings revealed that application of muscarine to NB neurons induced a GIRK current, and this GIRK current was also inhibited by SP. Thus, SP inhibits both KirNB and GIRKs. We conclude that the excitatory transmitter SP has two types of Kirs as its effectors: the constitutively active, G{beta}{gamma}-independent KirNB channel and the G{beta}{gamma}-dependent GIRK.
