Ion channels in axon and Schwann cell membranes at paranodes of mammalian myelinated fibers studied with patch clamp

Abstract

While recent studies have established the presence of voltage-gated ion channels on Schwann cells in culture and on freshly isolated fibers from mature mammals, an important issue not yet explored is whether Schwann cell channels are regionally specialized. In the nodal region, the intimate association between the Schwann cell and its axon suggests that this is a likely site for functional specialization. Here, we examine whether there is a localized expression of channels in the Schwann cell paranodal regions, in a manner similar to that already shown for the nodal axon. Cell-attached and outside-out patch-clamp recordings were made from paranodal regions of rat myelinated sciatic nerve fibers where the myelin on both sides of the node was retracted by enzymatic treatment. Even though no myelin was visible on the surface of the retracted paranode, significant portions of this surface were found to stain positively with a marker (anti-galactocerebroside) for Schwann cell membranes, suggesting that part of the axon still was covered by glial membranes. Using Lucifer yellow in the recording pipettes, we observed that the dye diffused into either axons or Schwann cells when the membrane under the tip was ruptured. Using this as a criterion to identify membranes obtained from retracted paranodes, we found delayed and inwardly rectifying potassium channels on both axon- and Schwann-derived patches. However, sodium channels were detected only in axon patches. This is the first report that voltage- gated glial channels are present in immediate vicinity to axons of the PNS. This finding, coupled with earlier reports that functional channels are absent in soma of mature myelinating Schwann cells, suggests that ion channels in these cells are regionally specialized for functional interaction with axons.

Potassium channel regulation in Schwann cells during early developmental myelinogenesis

“…It is tempting to speculate that the same type of potassium channel also is linked to Schwann cell proliferation during normal development. Indeed, when neonatal Schwann cells in culture are stimulated to divide, an outward rectifying potassium current is enhanced (Wilson and Chiu, 1988). Interestingly, in the present study, the decline in K, currents at the soma of developing cells correlates roughly with the known decline in proliferation measured in newborn rat sciatic nerves (Friede and Samorajski, 1968).…”

“…Preliminary results suggest a subtle difference. In vitro, multiple mitogens appear effective in stimulating Schwann cell outward currents and outward currents can appear in culture without axonal contact (Wilson and Chiu, 1988). In contrast, inward rectifying currents have not been observed in culture conditions.…”

Mislocalization of Kir channels in malignant glia

“…More detailed studies suggest that K ir channel expression correlates positively with cell differentiation, and K ir activity appears to be absent in proliferating glial cells. This relationship of K ir channel expression and cell differentiation has been demonstrated in astrocytes (MacFarlane and , Schwann cells (Wilson and Chiu, 1990;Konishi, 1994), Müller cells (Bringmann et al, 2000), and oligodendrocytes (Sontheimer et al, 1989;Barres et al, 1990) and thus appears to be a general feature of all glial cells. Intriguingly, changes in the expression and/or activity of K ir channels occur irrespective of how the change in differentiation state is initiated.…”

“…We (MacFarlane and Sontheimer, ,2000a and others (Wilson and Chiu, 1990;Konishi, 1994;Bringmann et al, 1999bBringmann et al, ,2000 have previously proposed that K ir channel activity correlates with the differentiation of astrocytes and their exit from the cell cycle. Treatment of immature astrocytes with the differentiation agent retinoic acid leads to a premature differentiation (MacFarlane and Sontheimer, 2000a) and also induces enhanced membrane expression of K ir channels.…”

Potassium Channels of Glial Cells: Distribution and Function

“…In Schwann cells, K + channels are not distributed homogeneously, but concentrated in the node of Ranvier (22). Kir2.1 and Kir2.3 were demonstrated to be localized at the microvilli of the nodes of Ranvier by using a specific antibody that recognizes both channels (23).…”