Evidence that glutamate mediates Axon‐to‐Schwann cell signaling in the squid

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Abstract
High-frequency stimulation (100 Hz) of isolated giant axons of the small squid Alloteuthis subulata and the large squid Loligo forbesi caused the periaxonal Schwann cell resting potential (Em = -40 mV) to hyperpolarize up to 11 mV in direct proportion to train duration and action potential amplitude. In both species, the Schwann cell also hyperpolarized up to 17 m V with the application of L-glutamate (10−9 to 10−6 M), in a dose-dependent manner. By contrast, in the presence of 10−8 M d-tubocurarine (d-TC) to block the cholinergic component of the Schwann cell response, Schwann cells depolarized 8–9 mV during electrical stimulation of the axon or application of L-glutamate. In the presence of 10−5 M 2-amino-4-phosphonobutyrate (2-APB), the hyperpolarization to glutamate and to axon stimulation was blocked, whereas the cholinergic (carbacholinduced) hyperpolarization was unaffected. In experiments with Alloteuthis, L-aspartate (10−7 M) also caused a Schwann cell hyperpolarization, but this was not blocked by 2-APB. In tests with glutamate receptor agonists and antagonists, quisqualate (10−5 M) produced a hyperpolarization blocked by 10−4 M L-glutamic acid diethylester (GDEE), which also blocked the response to axonal stimulation. Kainic acid (10−4 M) also caused a hyperpolarization, but n-methyl-D-aspartate (NMDA; 10−4 M), ibotenate (10−5 M), α-amino-3 hydroxy-5-methyl-isoxazole proprionate (AMPA; 10−4M), and isethionate (10−5M) had no effect. The results suggest that glutamate is a mediator of communication between the active axon and its surrounding Schwann cells and, by acting on quisqualate/kainate (i.e., non-NMDA) glutamate receptors, causes depolarization of the Schwann cell membrane. This depolarization in turn appears to activate cholinergic mechanisms in the Schwann cell that result in a secondary, long-lasting Schwann cell hyperpolarization. The function of the hyperpolarization is presently not well understood, but a contribution to regulation of the [K+] in the periaxonal microenvironment is proposed.