To study a possible involvement of inwardly rectifying K+4.1 (K(ir) 4.1) channels in neural cell development, RT-PCR, immunocytochemistry and whole-cell patch-clamp techniques were used to assess expression of K(ir) 4.1 channels in proliferating and differentiated NG108-15 cells. RT-PCR revealed co-expression of K(ir) 4.1 and rat ether-a-go-go-related gene (R-ERG) mRNAs in both proliferating and differentiated cells. The relative K(ir) 4.1 mRNA concentration increased markedly as cells progressed from undifferentiated to differentiated cells. K(ir) 4.1-immunoreactivity was barely detectable in undifferentiated cells, but clearly detected in differentiated cells, indicating that K(ir) 4.1 gene and protein expressions are developmentally regulated. However, corresponding K(ir) 4.1 current could not be detected in differentiated cells using whole-cell patch-clamp recording. The 'silent' channel/receptor, often found in tumor cells, may carry genetic defects, which prevent functional expression of the channel. NG108-15 may serve as unique model for studying the relationship between the expression of an ion channel gene and the electrophysiological phenotype it encodes.
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