Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain.
The members of the three subfamilies (eag, erg, and elk) of the ether-a-go-go (EAG) family of potassium channel pore-forming subunits express currents that, like the M-current (I(M)), could have considerable influence on the subthreshold properties of neuronal membranes, and hence the control of excitability. A nonradioactive in situ hybridization (NR-ISH) study of the distribution of the transcripts encoding the eight known EAG family subunits in rat brain was performed to identify neuronal populations in which the physiological roles of EAG channels could be studied. These distributions were compared with those of the mRNAs encoding the components of the classical M-current (Kcnq2 and Kcnq3). NR-ISH was combined with immunohistochemistry to specific neuronal markers to help identify expressing neurons. The results show that each EAG subunit has a specific pattern of expression in rat brain. EAG and Kcnq transcripts are prominent in several types of excitatory neurons in the cortex and hippocampus; however, only one of these channel components (erg1) was consistently expressed in inhibitory interneurons in these areas. Some neuronal populations express more than one product of the same subfamily, suggesting that the subunits may form heteromeric channels in these neurons. Many neurons expressed multiple EAG family and Kcnq transcripts, such as CA1 pyramidal neurons, which contained Kcnq2, Kcnq3, eag1, erg1, erg3, elk2, and elk3. This indicates that the subthreshold current in many neurons may be complex, containing different components mediated by a number of channels with distinct properties and neuromodulatory responses.
Saganich
M J
MJ
Department of Physiology and Neuroscience and Department of Biochemistry, New York University School of Medicine, New York, New York 10016.
Machado
E
E
Rudy
B
B
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D008297:Male; D005810:Multigene Family; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012684:Sensory Thresholds / Q000502:physiology
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; C496886:Kcnh1 protein, rat; C402401:Kcnh5 protein, rat; C109501:Kcnh7 protein, rat; C496915:Kcnq2 protein, rat; C496918:Kcnq3 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D012333:RNA, Messenger