A novel neurotransmitter-independent communication pathway between axons and glial cells

Recent studies have provided evidence that transmitters released by neurons can activate glial receptors and stimulate calcium signalling in glial cells. Glial calcium signalling, in turn, may affect neuronal performance such as long-term changes in synaptic efficacy. Olfactory ensheathing cells (OECs) are a special glial cell type in vertebrates and insects and promote axon growth in the developing and mature nervous system. Physiological properties of OECs, however, have not been studied so far in detail. We measured changes in the calcium concentration in OECs of the moth Manduca sexta, in situ and in vivo. Electrical stimulation of olfactory receptor neurons in pupae or odour stimulation of receptor neurons in adults resulted in calcium transients in OECs. Olfactory receptor axons release acetylcholine; however, application of acetylcholine or other transmitters such as glutamate, GABA or nitric oxide did not induce calcium transients in OECs. Upon nerve stimulation, extracellular potassium rose by several millimolar as measured with potassium-sensitive microelectrodes. When potassium in the perfusion saline was increased from 4 to 10 mM or higher, voltage-dependent calcium transients in OECs that resembled stimulation-induced calcium transients were evoked. Blocking neuronal potassium channels with TEA reduced both the stimulation-induced increases in extracellular potassium and the calcium transients in OECs, whereas calcium transients in receptor axons were augmented. Our results show for the first time that accumulation of potassium, released by electrically active axons, is sufficient to evoke voltage-dependent calcium influx into glial cells, whereas neurotransmitters appear not to be involved in this neuron-glia communication in Manduca.