Voltage-dependent sodium and potassium channels in mammalian cultured Schwann cells.

Abstract

Cultured Schwann cells from sciatic nerves of newborn rabbits and rats have been examined with patchclamp techniques. In rabbit cells, single sodium and potassium channels have been detected with single channel conductances of 20 pS and 19 pS, respectively. Single sodium channels have a reversal potential within 15 mV of ENa, are blocked by tetrodotoxin, and have rapid and voltage-independent inactivation kinetics. Single potassium channels show current reversal close to EK and are blocked by 4-aminopyridine. From these results, and from comparisons of single-channel and whole-cell data, we show that these Schwann cells contain voltage-dependent sodium and potassium channels that are similar in most respects to the corresponding channels in mammalian axonal membranes. Cultured rat Schwann cells also have sodium channels, but at a density about 1/10th that of rabbit cells, a result in agreement with saxitoxin binding experiments on axon-free sectioned nerves. Saxitoxin binding to cultured cells suggests that there are up to 25,000 sodium channels in a single rabbit Schwann cell. We speculate that in vivo Schwann cells in myelinated axons might act as a local source for sodium channels at the nodal axolemma.Soon after a rat sciatic nerve is cut and allowed to degenerate, the ability of the distal degenerated stump to bind saxitoxin (STX), which has been widely used as a specific marker for the voltage-dependent sodium channels of excitable tissue, virtually completely disappears (1). However, in the rabbit sciatic nerve under the same conditions, the axon-free degenerated stump is found to bind substantial amounts of the toxin (1). This latter binding of STX increases during the several days immediately following sectioning, a time during which Schwann cells proliferate in the distal region and occupy the space vacated by the degenerating axons. Squid Schwann cells (2) and human glial cells (3) are already known to possess sodium channels that are opened by veratridine and blocked by tetrodotoxin (TTX). However, neither these latter experiments (which measured the entry of 22Na into cells) nor the STX experiments provide unequivocal evidence for the presence of voltage-dependent sodium channels of the kind necessary for excitability.Electrophysiological experiments using the patch-clamp technique have already shown that in rat cultured Schwann cells there are both anion-selective and cation-selective channels (4, 5). The latter, however, are calcium-activated, show no selectivity for sodium compared to potassium, and lack the characteristic voltage dependence of the sodium channels found in excitable tissues. This latter finding is consistent with the earlier finding of a lack of STX binding capacity of the Schwann cells in rat distal degenerated stumps (1). The present experiments show by contrast that rabbit Schwann cells do indeed possess a relatively high density of voltage-dependent sodium channels, in conformity with the findings of the earlier experiments that they bind STX avidly (1). They also pos...

Potassium channel regulation in Schwann cells during early developmental myelinogenesis

“…In contrast to the K,, channel, this channel activates only at potentials approximately 25 mV positive to the resting potential and carries both inward and outward current. In instances where discrete channel openings can be discerned, the slope conductance of a single channel is estimated to be about 13 pS, in agreement with the conductance noted by Shrager et al (1985) for Schwann cell delayed rectifiers. No detailed kinetic analysis of this channel is pursued.…”

“…We focused only on voltage-gated potassium channels in cells visibly beginning to elaborate myelin and found not only an outward rectifying potassium channel which resembles that described in previous studies of Schwann cells (Chiu et al, 1984;Shrager et al, 1985;Chiu, 1987Chiu, , 1988Chiu and Wilson, 1989), but also an inward rectifying potassium channel which previously has not been described for Schwann cells. Both channels disappear from the soma as myelination proceeds.…”

“…However, patch-clamp recordings recently have provided evidence for the existence of neuronallike, voltage-gated ion channels in mammalian Schwann cells under cultured conditions (Chiu et al, 1984;Gray and Ritchie, 1985;Shrager et al, 1985), hinting that the Schwann cell's role may be more active than the traditional view implies. Already, accumulating evidence has revealed an interesting relation between channel expression and cell phenotype.…”

Immunolocalisation of sodium channel NaG in the intact and injured human peripheral nervous system

“…Whilst voltage-gated sodium channels are well described in excitable neuronal tissues, a number of studies have provided evidence for their presence in central and peripheral glia (Bevan et al 1985 ;Schrager et al 1985 ;Chiu, 1987 ;Barres et al 1990 ;Sontheimer et al 1991). Glial sodium channels exhibit similar but not identical properties to those of neuronal sodium channels ; differences exist in terms of channel kinetics (Barres et al 1990) and sensitivity to neurotoxins such as tetrodotoxin (TTX) and saxitoxin (Couraud et al 1986).…”

“…Hinson et al (1997) demonstrated that DRG neurons expressed significantly higher levels of NaG transcripts when cultured in the presence of Schwann cells compared with control DRG neurons ; the higher levels were associated with increased neuronal sodium channel density. It has also been suggested that Schwann cells may donate sodium channels to peripheral axons (Schrager et al 1985).…”