Heteromultimeric delayed-rectifier K+ channels in Schwann cells: Developmental expression end role in cell proliferation

Schwann cells (SCs) are responsible for myelination of nerve fibers in the peripheral nervous system. Voltage-dependent K+ currents, including inactiv ating A-type (K-A), delayed-rectifier (K-D), and inward-rectifier (K-IR) K channels, constitute the main conductances found in SCs. Physiological stu dies have shown that K-D channels may play an important role in SC prolifer ation and that they are downregulated in the soma as proliferation ceases a nd myelination proceeds. Recent studies have begun to address the molecular identity of K+ channels in SCs. Here, we show that a large repertoire of K f channel a subunits of the Shaker (Kv1.1, Kv1.2, Kv1.4, and Kv1.5), Shab ( Kv2.1), and Shaw (Kv3.1b and Kv3.2) families is expressed in mouse SCs and sciatic nerve. We characterized heteromultimeric channel complexes that con sist of either Kv1.5 and Kv1.2 or Kv1.5 and Kv1.4. In postnatal day 4 (P4) sciatic nerve, most of the Kv1.2 channel subunits are involved in heteromul timeric association with Kv1.5. Despite the presence of Kv1.1 and Kv1.2 a s ubunits, the K+ currents were unaffected by dendrotoxin I (DTX), suggesting that DTX-sensitive channel complexes do not account substantially for SC K -D currents. SC proliferation was found to be potently blocked by quinidine or 4-aminopyridine but not by DTX. Consistent with previous physiological studies, our data show that there is a marked downregulation of all K-D cha nnel alpha subunits from P1-P4 to P40 in the sciatic nerve. Our results sug gest that K-D currents are accounted for by a complex combinatorial activit y of distinct K+ channel complexes and confirm that K-D channels are involv ed in SC proliferation.