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The Journal of Neuroscience, November 1, 1998, 18(21):8740-8750
Differences in Ca2+ Channels Governing Generation of
Miniature and Evoked Excitatory Synaptic Currents in Spinal Laminae I
and II
Juping
Bao,
Jing James
Li, and
Edward R.
Perl
Department of Cell and Molecular Physiology, University of
North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599-7545
Many neurons of spinal laminae I and II, a region concerned with
pain and other somatosensory mechanisms, display frequent miniature
"spontaneous" EPSCs (mEPSCs). In a number of instances, mEPSCs
occur often enough to influence neuronal excitability. To compare
generation of mEPSCs to EPSCs evoked by dorsal root stimulation
(DR-EPSCs), various agents affecting neuronal activity and
Ca2+ channels were applied to in
vitro slice preparations of rodent spinal cord during
tight-seal, whole-cell, voltage-clamp recordings from laminae I and II
neurons. The AMPA/kainate glutamate receptor antagonist CNQX (10-20
µM) regularly abolished DR-EPSCs. In many neurons CNQX
also eliminated mEPSCs; however, in a number of cases a proportion of
the mEPSCs were resistant to CNQX suggesting that in these instances
different mediators or receptors were also involved.
Cd2+ (10-50 µM) blocked evoked EPSCs
without suppressing mEPSC occurrence. In contrast,
Ni2+ ( 100 µM), a low-threshold
Ca2+ channel antagonist, markedly decreased mEPSC
frequency while leaving evoked monosynaptic EPSCs little changed.
Selective organic antagonists of high-threshold (HVA)
Ca2+ channels, nimodipine, -Conotoxin GVIA, and
Agatoxin IVA partially suppressed DR-EPSCs, however, they had little or
no effect on mEPSC frequency. La3+ and mibefradil,
agents interfering with low-threshold Ca2+ channels,
regularly decreased mEPSC frequency with little effect on fast-evoked
EPSCs. Increased [K+]o (5-10
mM) in the superfusion, producing modest depolarizations, consistently increased mEPSC frequency; an increase suppressed by
mibefradil but not by HVA Ca2+ channel antagonists.
Together these observations indicate that different
Ca2+ channels are important for evoked EPSCs and
mEPSCs in spinal laminae I and II and implicate a low-threshold type of
Ca2+ channel in generation of mEPSCs.
Key words:
mEPSCs; EPSCs; LVA Ca2+ channels; spinal laminae I and II; spinal dorsal horn; rodent; mibefradil; La3+
Copyright © 1998 Society for Neuroscience 0270-6474/98/18218740-11$05.00/0
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