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 microM acetylcholine were well described by two exponentials, with fast and slow time constants of 0.53 +/- 0.12 and 16.7 +/- 2.2 ms (means +/- s.e. mean) respectively. 3. The duration of the slow open time constant was increased by low concentrations of pentobarbitone (up to 1 microM), and thereafter decreased with higher concentrations (10-50 microM) 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.
Liu
G J
GJ
Department of Pharmacology, University of Western Australia, Nedlands, Australia.
Madsen
B W
BW
D000818:Animals; D002642:Chick Embryo; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*
D006993:Hypnotics and Sedatives; D007473:Ion Channels; D011978:Receptors, Nicotinic; D010424:Pentobarbital