We examined potassium channel gene expression of two members of the Shaker subfamily, MK1 and MK2, in sciatic nerves from rats and mice. In Northern blot analysis, MK1 and MK2 probes detected single transcripts of approximately 8 kb and approximately 9.5 kb, respectively, in sciatic nerve and brain from both species. Polymerase chain reaction amplification of a cDNA library of cultured rat Schwann cells using MK1- and MK2- specific primers produced DNA fragments that were highly homologous to MK1 and MK2. To determine whether these channel genes were axonally regulated, we performed Northern blot analysis of developing, permanently transected, and crushed rat sciatic nerves. The mRNA levels for both MK1 and MK2 increased from P1 to P15 and then declined modestly. Permanent nerve transection in adult animals resulted in a dramatic and permanent reduction in the mRNA levels for both MK1 and MK2, whereas normal levels of MK1 and MK2 were restored when regeneration was allowed to occur following crush injury. In all cases, MK1 and MK2 mRNA levels paralleled that of the myelin gene P0. Elevating the cAMP in cultured Schwann cells by forskolin, which mimics axonal contact but not myelination, did not induce detectable levels of MK1 and MK2 mRNA by Northern blot analysis. Further, the level of MK1 mRNA in the vagus nerve, which contains relatively fewer myelinating Schwann cells and relatively more non-myelinating Schwann cells than the sciatic nerve, is reduced relative to the sciatic nerve. In conclusion, we have identified two Shaker-like potassium channel genes in sciatic nerves whose expressions are regulated by axons. We suggest that MK1 and MK2 mRNA are expressed in high levels only in myelinating Schwann cells and that these Shaker-like potassium channel genes have specialized roles in these cells.