Voltage-dependent block of excitatory amino acid currents by pentobarbital

The blocking of excitatory amino acid currents by pentobarbital was studied in cultured hippocampal neurons. Peak amino acid currents were plotted against holding potential prior to and following bath applications of pentobarbital. The divalent cation Mg2+ was not added either to the recording or extracellular solution. As a consequence, current-voltage curves were approximately linear regardless of the excitatory amino acid employed. Kainic acid (KAI) currents were more sensitive to blockade by pentobarbital than were those activated by L-aspartic acid (L-Asp). However, blockade of all currents (including those for KAI) was more pronounced at hyperpolarized values than at comparable depolarized potentials (i.e. in the presence of the same driving force). Furthermore, the voltage-dependence of the pentobarbital blockade was greater for L-Asp than for KAI. Since pentobarbital is neutrally charged (or weakly negative) under the present recording conditions, the voltage-sensitivity of its block must arise from the influence of membrane field upon the site of the block rather than upon the access of the blocking molecule to this site.