Heterogeneity in EC50 and nH of GABAA receptors on dorsal root ganglion neurons freshly isolated from adult rats.
GABA activates a Cl- current through the GABAA receptor/ionophore complex that influences excitability of neurons. Studies using expression of cloned cDNAs coding for different GABAA receptor/ionophore subunits suggest that the EC50 and Hill coefficient for GABA are influenced by subunit composition. However, no direct evidence for such heterogeneity has been reported for vertebrate neurons. I have investigated the heterogeneity of EC50 and Hill coefficients (nH) of isolated dorsal root ganglion neurons using the whole-cell patch clamp technique. The EC50 for GABA varied from 26 to 107 microM among neurons. nH calculated from the logistic equation varied from 1.18 to 2.0. A negative correlation was found between the EC50 and nH (r = -0.81). Both nH and EC50 differed between some cells. However, in some instances, nH differed between cells while EC50 values were similar, and in other cells, EC50 values differed and nH was similar. In addition, when cells were categorized according to action potential shape, the EC50 and Hill coefficients differed among cell types in some instances and were similar in other instances. These findings demonstrate that different pharmacological profiles for GABA can be observed in adult mammalian neurons. Selective distribution of such pharmacological subtypes of GABAA receptors may contribute to control of neuronal excitability.
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Neurogen Corporation, Branford, CT 06405.
D000818:Animals; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid