Choline and acetylcholine have similar kinetic properties of activation and desensitization on the alpha 7 nicotinic receptors in rat hippocampal neurons
A. Mike et al., Choline and acetylcholine have similar kinetic properties of activation and desensitization on the alpha 7 nicotinic receptors in rat hippocampal neurons, BRAIN RES, 882(1-2), 2000, pp. 155-168
The alpha7-type nicotinic acetylcholine receptor (nAChR) was recently found
to be both fully activated and desensitized by choline, in addition to ACh
. In order to understand the combined effects of the two agonists on alpha7
nAChR-mediated neuronal signaling, the kinetics of the receptor-channel's
interaction with ACh and choline was examined. To this end, whole-cell and
single-channel currents evoked by Fast-switching pulses of the agonists wer
e recorded in rat hippocampal neurons in culture. Currents evoked by equief
fective concentrations of choline and ACh were very similar, except that ch
oline-evoked currents decayed more quickly to the baseline after removal of
the agonist, and that recovery from desensitization was faster with cholin
e. The conductance of channels activated by choline and ACh was 91.5+/-8.5
and 82.9+/-11.6 pS, respectively. The mean apparent channel open times were
close to 100 mus, with both agonists. After a 4-s exposure to concentratio
ns up to 80 muM ACh or 600 muM choline, the extent of desensitization and t
he cumulative charge flow carried by the channels increased in the same pro
portion, until reaching a maximum. At higher concentrations of either agoni
st, the cumulative charge started decreasing with concentration, reflecting
further desensitization. Kinetic modeling suggested that alpha7 nAChRs hav
e at least two non-equivalent paths to desensitized states, and that cholin
e dissociates faster than ACh from the receptor. Our results established th
at the main difference between choline and ACh is of affinity, and support
the concept that the switching of endogenous agonist may change the desensi
tization-resensitization dynamics of alpha7 nAChRs. (C) 2000 Elsevier Scien
ce B.V. All rights reserved.