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The Journal of Neurophysiology Vol. 85 No. 2 February 2001, pp. 580-593
Copyright ©2001 by the American Physiological Society
Division of Neurophysiology, Department of Medical Physiology, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark
Kjaerulff, Ole and
Ole Kiehn.
5-HT Modulation of Multiple Inward Rectifiers in Motoneurons in
Intact Preparations of the Neonatal Rat Spinal Cord. J. Neurophysiol. 85: 580-593, 2001. This study
introduces novel aspects of inward rectification in neonatal rat spinal
motoneurons (MNs) and its modulation by serotonin (5-HT). Whole cell
tight-seal recordings were made from MNs in an isolated lumbar spinal
cord preparation from rats 1-2 days of age. In voltage clamp,
hyperpolarizing step commands were generated from holding potentials of
50 to
40 mV. Discordant with previous reports involving slice
preparations, fast inward rectification was commonly expressed and in
44% of the MNs co-existed with a slow inward rectification related to
activation of Ih. The fast inward
rectification is likely caused by an
IKir. Thus it appeared around
EK and was sensitive to low
concentrations (100-300 µM) of Ba2+ but not to
ZD 7288, which blocked Ih. Both
IKir and
Ih were inhibited by
Cs2+ (0.3-1.5 mM). Extracellular addition of
5-HT (10 µM) reduced the instantaneous conductance, most strongly at
membrane potentials above EK. Low
[Ba2+] prevented the 5-HT-induced
instantaneous conductance reduction below, but not that above,
EK. This suggests that 5-HT inhibits IKir, but also other instantaneous
conductances. The biophysical parameters of
Ih were evaluated before and under
5-HT. The maximal Ih conductance,
Gmax, was 12 nS, much higher than
observed in slice preparations. Gmax
was unaffected by 5-HT. In contrast, 5-HT caused a 7-mV depolarizing
shift in the activation curve of Ih.
Double-exponential fits were generally needed to describe Ih activation. The fast and slow time
constants obtained by these fits differed by an order of magnitude.
Both time constants were accelerated by 5-HT, the slow time constant to
the largest extent. We conclude that spinal neonatal MNs possess
multiple forms of inward rectification.
Ih may be carried by two spatially
segregated channel populations, which differ in kinetics and
sensitivity to 5-HT. 5-HT increases MN excitability in several ways,
including inhibition of a barium-insensitive leak conductance,
inhibition of IKir, and enhancement of
Ih. The quantitative characterization of these effects should be useful for further studies seeking to
understand how neuromodulation prepares vertebrate MNs for concerted
behaviors such as locomotor activity.
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