The effect of dimethyl sulfoxide on the neuronal excitability and cholinergic transmission in Aplysia ganglion cells.

The effects of DMSO on single nerve cells of Aplysia were investigated by various electrophysiological methods. 1. Although the increase in permeability of the biological membranes produced by DMSO has been well documented, we found that DMSO at concentration of less than 20% actually decreases the permeability of the neuronal membranes, probably toward potassium and chloride ions. This change in ionic permeability reversibly depolarizes the resting membranes and makes the neurons more excitable. 2. The falling phase of the spike is prolonged by 8% DMSO, because it blocks the active increase in potassium permeability. This change suppresses the high frequency discharge, because the refractory period of each spike is increased. Neither the rising phase nor the absolute firing level is appreciably altered by DMSO when these are examined after the depolarization is cancelled. 3. Dilute DMSO (less than 1%) facilitates cholinergic trasmission because it blocks ACh-esterase activity. DMSO at concentrations of more than 10% ultimately blocks cholinergic transmission entirely, because it also depresses cholinoceptive receptor activity (probably by allosteric interaction). The action of 1-10% DMSO is complicated, because both facilitatory and inhibitory effects take place at the same time. 4. In cholinergic synapses, excitatory transmission is more susceptible to DMSO than inhibitory transmission. This is because the activity of the excitatory receptor is blocked more readily than that of the inhibitory receptor. The depressing effects of DMSO are not specific to the cholinergic system, however, since the activities of GABA and glutamate receptors are similarly depressed.