Two different inward rectifier K+ channels are effectors for transmitter-induced slow excitation in brain neurons.
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 Gbeta(1gamma2) to inside-out patches induced activity of a second type of Kir (GIRK). Application of Gbeta(1gamma2), however, did not change the KirNB activity. Sequestering Gbeta(1gamma2) with Galpha(i2) 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, Gbetagamma-independent KirNB channel and the Gbetagamma-dependent GIRK.
Bajic
D
D
Department of Anatomy and Cell Biology, University of Illinois, Chicago, IL 60612, USA.
Koike
M
M
Albsoul-Younes
A M
AM
Nakajima
S
S
Nakajima
Y
Y
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D010766:Phosphorylation; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D013373:Substance P / Q000494:pharmacology
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C410342:GNG2 protein, human; D018377:Neurotransmitter Agents; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011518:Proto-Oncogene Proteins; D013373:Substance P; D019204:GTP-Binding Proteins; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498017:Gnai2 protein, rat