title: Differences in Ca2+ channels governing generation of miniature and evoked excitatory synaptic currents in spinal laminae I and II.
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 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 microM) 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 microM) blocked evoked EPSCs without suppressing mEPSC occurrence. In contrast, Ni2+ (</=100 microM), 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, omega-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.
authors.affiliation: Department of Cell and Molecular Physiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599-7545, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bao
authors.forename: J J
authors.initials: JJ
authors.lastname: Li
authors.forename: E R
authors.initials: ER
authors.lastname: Perl
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D006224:Cricetinae; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005727:Ganglia, Spinal / Q000378:metabolism; D066298:In Vitro Techniques; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D002104:Cadmium; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D009532:Nickel; D011188:Potassium