Differences in Ca2+Channels Governing Generation of Miniature and Evoked Excitatory Synaptic Currents in Spinal Laminae I and II

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Abstract
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 toin vitroslice 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, ω-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.