Biphasic effect of pentobarbitone on chick myotube nicotinic receptor channel kinetics

1 The modulatory action of pentobarbitone on chick myotube nicotinic acetylcholine receptor kinetics was studied by the patch clamp technique, particularly focussing on effects at low concentrations. 2 Open time sojourn distributions of foetal-type receptors recorded at room temperature (22-24 degrees C) in cell-attached mode in the presence of 0.2 mu M acetylcholine were well described by two exponentials, with fast and slow time constants of 0.53+/-0.12 and 16.7+/-2.2 ms (mean+/-s.e.mean) respectively. 3 The duration of the slow open time constant was increased by low concentrations of pentobarbitone (up to 1 mu M), and thereafter decreased with higher concentrations (10-50 mu M) in a concentration-dependent manner. 4 Complementary evidence for the stimulatory effect of pentobarbitone on open time was obtained (i) by using a backfill technique where drug concentration at the patch gradually increases over time, and (ii) through use of perfused outside-out preparations where receptors in the same patch were successively exposed to acetylcholine in the absence and presence of pentobarbitone. 5 The dual action of pentobarbitone on channel kinetics probably indicates that an allosteric interaction mechanism is involved rather than simple steric channel blockade.