EPILEPTIFORM ACTIVITY IN THE HIPPOCAMPUS PRODUCED BY TETRAETHYLAMMONIUM

1. The epileptiform discharges in the CA3 region of the rat hippocampal slice produced by bath application of the potassium channel blocker tetraethylammonium (TEA) were investigated. The effects of a convulsant (5 mM) and subconvulsant (0.5 mM) concentration of TEA on the mossy fiber-evoked synaptic currents were studied by the use of voltage-clamp techniques to determine whether TEA, like 4-aminopyridine (4-AP), another potassium channel blocker and convulsant, increased both inhibitory and excitatory components of the synaptic response. 2. At extracellular potassium concentrations of 2.5 mM, TEA (5 mM) was found to produce spontaneously occurring epileptiform discharges that could be recorded extracellularly. The intracellular correlate of the epileptiform discharge, the paroxysmal depolarizing shift (PDS), could be reversed in polarity by depolarizing the membrane and was associated with a large increase in membrane conductance. These results suggest that a synaptically mediated potential underlies the generation of the epileptiform discharge. 3. The reversal potential for the PDS was dependent on the time, relative to the extracellularly recorded field discharge, at which the measurement was made. In current clamp the mean reversal potential of the PDS measured at the midpoint of the extracellular discharge was -3.3 ± 2.9 (SE) mV (n = 9). The reversal potential of the PDS was considerably more negative when measured either before or after the midpoint of the extracellular discharge, suggesting the presence of an inhibitory synaptic component. In voltage clamp similar results were obtained and a large conductance change was found to be associated with the PDS. These results suggest that the synaptic conductance associated with the PDS has both inhibitory and excitatory components. 4. TEA increased significantly the mossy fiber-evoked, early-inhibitory conductance. A convulsant concentration (5 mM) increased the conductance measured 15 ms after the stimulus from 39.7 ± 8.7 to 87.2 ± 8.0 nS (n = 6). The reversal potential associated with the conductance depolarized from -68.3 ± 3.4 to -58.3 ± 4.0 mV after 5 mM TEA. A subconvulsant concentration of TEA (0.5 mM) also increased the conductance of the mossy fiber-evoked response at 15 ms after the stimulus from 49.5 ± 3.1 to 63.1 ± 6.1 nS (n = 4) without an associated shift in reversal potential. 5. The late-inhibitory component of the mossy fiber-evoked response, when present, was increased by 5 mM TEA and unchanged by 0.5 mM TEA. 6. The excitatory mossy fiber-evoked synaptic current was studied in the presence of picrotoxin and was found to be increased and prolonged by 5 mM TEA. The peak measured conductance increased from 17.4 ± 2.0 to 46.3 ± 5.1 nS (n = 6) after 5 mM TEA, without a significant shift in reversal potential. A subconvulsant concentration of TEA (0.5 mM) increased the measured mossy fiber-evoked conductance change from 17.9 ± 1.7 to 31.0 ± 3.8 nS (n = 4) and was associated with a slight, but statistically significant, hyperpolarization in the reversal potential (-10.9 ± 1.9 to -13.8 ± 1.4 mV). 7. The input resistance and the membrane potential of pyramidal neurons were not significantly affected by either 0.5 or 5 mM TEA at times that the I-V relationship of the mossy fiber-evoked synaptic responses were obtained. The increase in the measured synaptic conductances produced by TEA appears to be a consequence of presynaptic effects. 8. TEA represents another example of a potassium channel blocker with convulsant properties. Although TEA and 4-AP presumably decrease different potassium current, they both are convulsants and are associated with an enhancement of both inhibitory and excitatory synaptic transmission in the hippocampus.