Electrophysiological study of tert-butylbicyclophosphorothionate-induced block of spontaneous chloride channels.

The action of TBPS (tert-butylbicyclophosphorothionate) on spontaneous chloride channels recorded from porcine pars intermediate lobe cells in primary culture has been studied. This compound, which binds specifically to the gamma-aminobutyric acidA (GABAA) receptor complex, is known as a channel-gating (non-competitive) GABA antagonist. The present results show that TBPS reduces spontaneous chloride channel activity in a dose-dependent manner, with an IC50 equal to 55 nM, which is a value comparable to its affinity for the GABAA binding sites. Single-channel analysis revealed that TBPS affects neither the amplitude nor the open time of these spontaneous channels but prolongs the longer closed times, resulting in a dramatic decrease in opening probability.