Effects of dithiothreitol, a sulfhydryl reducing agent, on CA1 pyramidal cells of the guinea pig hippocampus in vitro.

The radioprotectant, dithiothreitol (DTT) has been shown to increase excitability in the hippocampal slice preparation. In the present study, intracellular recording techniques were used to further examine the actions of DTT. Electrophysiological recordings from CA1 pyramidal cells were obtained prior to, during and after DTT exposure. DTT caused a small depolarization without altering membrane resistance. DTT induced spontaneous firing and occasional burst firing in normally silent neurons. These effects were accompanied by a reduction in spike frequency adaptation but no change in the afterhyperpolarization following a train of action potentials. Following DTT exposure, orthodromic stimulation produced multiple firing. Subthreshold excitatory postsynaptic potentials (EPSPs) were significantly prolonged. Isolating the CA1 subfield, attenuated the prolongation of the EPSP by DTT. Recurrent inhibitory postsynaptic potentials were unaffected by DTT. The actions of DTT are likely to result from DTT-induced reduction of disulfide bonds since the reduced form of DTT does not cause a similar hyperexcitability.