REGULATORY MECHANISMS FOR THE DENSITY AND PROPERTY OF K^+ CHANNELS

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Channel density is a fundamental factor determining neuronal firing, and is primarily regulated during development through transcriptional and translational regulation. In adult rats, striatal cholinergic interneurons have a prominent A-type current and co-express Kv4.1 and Kv4.2 mRNAs. We have previously shown that Kv4.2 plays an essential role in producing the A-type current in striatal cholinergic interneurons. In a semi quantitative study, we found that the developmental time course of A-type current and Kv4.2 mRNA could be well described by a transcriptional and translation mechanism, together with degradation of channel proteins and mRNAs. The regulation of channel density is thus primarily determined by the rates of transcription, translation, and degradation. Here we have developed an in vitro preparation with which striatal slices could be kept alive for several days. Using this preparation, we studied the turnover rate of A-type channel protein and Kv4.2 mRNA by adding blockers of protein synthesis and transcription blockers. We found that A-type current was reduced to half value in one day fro slices from two weeks old rats. However, it took two days for currents in three weeks old rats to be reduced to half value. Thus the turnover of channel protein is likely to be age dependent. The half life of Kv4.2 mRNA was fund to be one day. The slice preparation developed in this study should be useful for further study on channel density regulation.Striatal cholinergic interneurons also express a delayed rectifier current. Candidate genes for the delayed rectifier have also been tested in this study.