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 s ubthreshold properties of neuronal membranes, and hence the control of exci tability. A nonradioactive in situ hybridization (NR-ISH) study of the dist ribution of the transcripts encoding the eight known EAG family subunits in rat brain was performed to identify neuronal populations in which the phys iological 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 t o specific neuronal markers to help identify expressing neurons. The result s show that each EAG subunit has a specific pattern of expression in rat br ain. EAG and Kcnq transcripts are prominent in several types of excitatory neurons in the cortex and hippocampus; however, only one of these channel c omponents (erg1) was consistently expressed in inhibitory interneurons in t hese 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 trans cripts, 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.