Journal of Neuroscience, Vol 14, 3835-3841, Copyright © 1994 by Society for Neuroscience
Terbium modulation of single gamma-aminobutyric acid-activated chloride channels in rat dorsal root ganglion neurons
JY Ma, E Reuveny and T Narahashi
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
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)