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The Journal of Neuroscience, June 1, 1998, 18(11):4050-4062
Neuronal Nicotinic Acetylcholine Receptors Are Blocked by
Intracellular Spermine in a Voltage-Dependent Manner
Ali Pejmun
Haghighi and
Ellis
Cooper
Department of Physiology, McGill University, Montréal,
Québec, Canada H3G 1Y6
A common feature of neuronal nicotinic acetylcholine receptors
(nAChRs) is that they conduct inward current at negative membrane potentials but little outward current at positive membrane potentials, a property referred to as inward rectification. Physiologically, inward
rectification serves important functions, and the main goal of our
study was to investigate the mechanisms underlying the rectification of
these receptors. We examined recombinant  3 4 and 42
neuronal nAChR subtypes expressed in Xenopus oocytes and
native nAChRs expressed on superior cervical ganglion (SCG) neurons.
Whole-cell ACh-evoked currents recorded from these receptors exhibited
strong inward rectification. In contrast, we showed that single-channel
currents from these neuronal nAChRs measured in outside-out patches
outwardly rectify. On the basis of recent findings that spermine, a
ubiquitous intracellular polyamine, confers rectification to glutamate
receptors and inwardly rectifying potassium channels, we investigated
whether spermine causes neuronal nAChRs to inwardly rectify. When
spermine was added to the patch electrode in outside-out recordings, it
caused a concentration- and voltage-dependent block of ACh-evoked
single-channel currents. Using these single-channel data and
physiological concentrations of intracellular spermine, we could
account for the inward rectification of macroscopic whole-cell
ACh-evoked conductance-voltage relationships. Therefore, we conclude
that the voltage-dependent block by intracellular spermine underlies
inward rectification of neuronal nAChRs. We also found that
extracellular spermine blocks both 34 and
42 receptors; this finding points to a
mechanism whereby increases in extracellular spermine, perhaps during
pathological conditions, could selectively block these receptors.
Key words:
neuronal nAChRs; sympathetic neurons; inward
rectification; single-channel currents; spermine; voltage-dependent
block; presynaptic modulation
Copyright © 1998 Society for Neuroscience 0270-6474/98/18114050-13$05.00/0
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