AXONS REGULATE THE EXPRESSION OF SHAKER-LIKE POTASSIUM CHANNEL GENES IN SCHWANN-CELLS IN PERIPHERAL-NERVE

We examined potassium channel gene expression of two members of the Sh aker subfamily, MK1 and MK2, in sciatic nerves from rats and mice. In Northern blot analysis, MK1 and MK2 probes detected single transcripts of similar to 8 kb and similar to 9.5 kb, respectively, in sciatic ne rve and brain from both species. Polymerase chain reaction amplificati on of a cDNA library of cultured rat Schwann cells using MK1- and MK2- specific primers produced DNA fragments that were highly homologous t o MK1 and MK2. To determine whether these channel genes were axonally regulated, we performed Northern blot analysis of developing, permanen tly transected, and crushed rat sciatic nerves. The mRNA levels for bo th MK1 and MK2 increased from P1 to P15 and then declined modestly. Pe rmanent nerve transection in adult animals resulted in a dramatic and permanent reduction in the mRNA levels for both MK1 and MK2, whereas n ormal levels of MK1 and MK2 were restored when regeneration was allowe d to occur following crush injury. In all cases, MK1 and MK2 mRNA leve ls paralleled that of the myelin gene Po. Elevating the cAMP in cultur ed Schwann cells by forskolin, which mimics axonal contact but not mye lination, did not induce detectable levels of MK1 and MK2 mRNA by Nort hern blot analysis. Further, the level of MK1 mRNA in the vagus nerve, which contains relatively fewer myelinating Schwann cells and relativ ely more non-myelinating Schwann cells than the sciatic nerve, is redu ced relative to the sciatic nerve. In conclusion, we have identified t wo Shaker-like potassium channel genes in sciatic nerves whose express ions are regulated by axons. We suggest that MK1 and MK2 mRNA are expr essed in high levels only in myelinating Schwann cells and that these Shaker-like potassium channel genes have specialized roles in these ce lls. (C) 1994 Wiley-Liss, Inc.