Terbium modulation of single gamma-aminobutyric acid-activated chloride channels in rat dorsal root ganglion neurons.
We have previously reported that lanthanides markedly potentiate the GABA-induced chloride current by acting at a distinct site on the GABAA receptor-channel complex (Ma and Narahashi, 1993a,b). These studies have now been extended to the single-channel level and changes in gating kinetics of GABAA receptor currents caused by 100 microM terbium (Tb3+) are reported. The GABA-induced currents were recorded from outside-out membrane patches isolated from rat dorsal root ganglion neurons in primary culture at a holding potential of -60 mV. At least two conductance levels were recorded, a main conductance of about 26 pS (70-80% of events) and a subconductance of about 19 pS (20-30% of events). These two conductances and the ratio of main- and subconductance state currents with respect to the number of events were not changed by Tb3+. The frequency of channel openings was also unchanged in the presence of Tb3+. The frequency histograms of open, close, and burst durations of the main-conductance state were best fitted by a sum of three exponential functions. All of the time constants remained unchanged by application of Tb3+ while the relative proportions of the longest open and burst duration time constants were increased and the relative proportion of longest closed time constant was decreased. We suggest that Tb3+ binds to an allosteric site on the GABAA receptor-channel complex to increase the apparent mean open time of the channel by increasing the affinity of GABA for the GABA binding site, and/or by shifting the distribution toward the open states so that the frequency of occurrence of longer open states is stabilized.(ABSTRACT TRUNCATED AT 250 WORDS)
Ma
J Y
JY
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
Reuveny
E
E
Narahashi
T
T
D000818:Animals; D000831:Animals, Newborn; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013725:Terbium / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018118:Chloride Channels; D013725:Terbium; D005680:gamma-Aminobutyric Acid