Control of myelination, axonal growth, and synapse formation in spinal cord explants by ion channels and electrical activity

Abstract

The involvement of axonal electrical activity and ion channels as mediators of neuron-glial communication during myelin formation has been tested in explant culture. Transverse slices of embryonic mouse spinal cord were maintained under conditions normally leading to extensive myelination. Axonal conduction was measured optically through the use of a voltage-sensitive dye. Glial development was at a very early stage at the time of plating, and oligodendrocyte precursor cells had not yet appeared. Spontaneous electrical activity was blocked either by tetrodotoxin or by elevation of external K+ concentrations. Myelin development was unaffected by tetrodotoxin and was also present, though quantitatively reduced, in elevated K+. Tetraethylammonium ion (TEA+), a blocker of many K+ channels, almost entirely eliminated myelination at a concentration of 1 mM, but axonal growth and conduction were unaffected. Synapse formation was followed both morphologically and functionally, and was altered neither by conduction block nor by 1 mM TEA+. It is concluded that in the spinal cord oligodendrocyte development and myelination can proceed in the absence of axonal action potentials, but ion channels, possibly in glial membranes, play an important role in these events.