Benzodiazepines both enhance gamma-aminobutyrate responses and decrease calcium action potentials in guinea-pig myenteric neurones.

Abstract

The effect of two benzodiazepines, midazolam and diazepam, was studied in guinea-pig myenteric neurones, using intracellular recording techniques. Both these benzodiazepines (100-300 pM) potentiated the rapidly desensitizing, bicuculline-sensitive depolarization, induced by alpha-aminobutyrate ionophoresis. Concentrations of midazolam and diazepam higher than 100 nM depressed the gamma-aminobutyrate-induced depolarization. The potentiating effect of the benzodiazepines was reversibly abolished by Ro 15-1788 (1-100 nM) and by pentylenetetrazol (100 microM). A second effect of midazolam and diazepam (100-300 pM) was a reversible depression of the amplitude and duration of the directly evoked action potential in 29% of neurones, without affecting membrane potential or conductance. The effect was very marked when electrodes were filled with CsCl, and was also seen in the presence of tetrodotoxin. In some but not all of these neurones, the amplitude and duration of the action potentials was reduced also by gamma-aminobutyrate (1-10 microM). Ro 15-1788 and pentylenetetrazol reversibly abolished the effect of benzodiazepines on the action potential, but not that of gamma-aminobutyrate. Thus, benzodiazepines have two effects on myenteric neurones. The first is an enhancement of the gamma-aminobutyrate response (activation of Cl conductance); the second is a depression of the calcium action potential, which appears to be independent of gamma-aminobutyrate.