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 mV with the application of L-glutamate (10-to MI, in a dose-dependent manner. By contrast, in the presence of lop8 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 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 M) also caused a Schwann cell hyperpolarization, but this was not blocked by2-APB.
In tests with glutamate receptor agonists and antagonists, quisqualate (lop5 M) produced a hyperpolarization blocked by M L-glutamic acid diethylester (GDEE), which also blocked the response to axonal stimulation. Kainic acid M) also caused a hyperpolarization, but n-methyl-D-aspartate (NMDA; l o p 4 M), ibotenate ( M), a-amino-3 hydroxy-5-methyl-isoxazole proprionate (AMPA; MI, and isethionate (lK5M) 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 quisqualatekainate (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. 0 1 9 8 9 Alan R. I.iss, Inc.
finally results in membrane hyperpolarization (Evans et al., 1985;Villegas, 1984). Octopamine acting through cyclic adenosine monophosphate (CAMP) (Reale et al., 1986) and vasoactive intestinal peptide (VIP) acting via