GTP- and GDP-analogues modulate an inwardly rectifying chloride channel in cultured hippocampal neurons

Three different GABA-insensitive Cl − channels could be resolved in cultured hippocampal neurons using the inside-out patch clamp configuration. The most commonly observed channel revealed an inward rectification with a chord conductance of 40 pS in symmetrical Cl − solutions at a membrane potential of −50 mV and had voltage sensitive gating kinetics. Channel openings were not observed in cell-attached patch, and after excision, several minutes of perfusion of the cytoplasmic side were required before detecting the first openings. The open state probability was increased by guanosine 5′- O -(3-thiotriphospate) (GTP-γ-S 10 −4 M) and reduced by guanosine 5′- O -(2-thiophosphate) (GDP-β-S 10 −4 M) suggesting its regulation by G proteins. This new identified chloride channel may account for the previously described voltage-sensitive, inward-rectifying whole cell Cl − current which was enhanced by adenosine in a pertussis toxin-sensitive manner.