title: Regulation of excitability in tonic firing substantia gelatinosa neurons of the spinal cord by small-conductance Ca(2+)-activated K(+) channels.
abstract: The excitability of substantia gelatinosa (SG) neurons in the spinal dorsal horn determines the processing of nociceptive information from the periphery to the central nervous system. Small conductance Ca(2+)-activated K(+) (SK) channels on neurons supply strong negative feedback control on neuronal excitability by affecting afterhyperpolarization (AHP). However, the role of SK channels in regulating tonic-firing SG neuron excitability remains elusive. In the present study, whole-cell recordings were conducted in SG neurons from acute spinal cord slices of adult rats. The SK channel opener 1-ethyl-2-benzimidazolinone (1-EBIO) attenuated spike discharges and increased AHP amplitudes; this effect was mimicked by a high Ca(2+) external solution. Systemic administration of 1-EBIO attenuated the thermal-induced nociception behavior. Conversely, the inhibition of SK channels with apamin, a specific SK channel inhibitor, increased neuronal excitability and decreased the AHP amplitudes; this effect was mimicked by a Ca(2+)-free external solution. Apamin increased excitatory synaptic transmission by increasing the amplitudes of evoked excitatory postsynaptic potentials (eEPSPs). This facilitation depended on N-methyl-d-aspartate (NMDA) receptors, extracellular Mg(2+) and intracellular Ca(2+). Voltage-gated Ca(2+) channels (VGCCs) were also involved in the apamin-induced effects. Strikingly, 1-EBIO action on decreasing excitability persisted in the presence of apamin, indicating that 1-EBIO manipulates SK channels via a pathway rather than via apamin-sensitive SK channels. The data reveal a previously uncharacterized mechanism for manipulating SG neuronal excitability by Ca(2+) conductances via both apamin-sensitive and apamin-insensitive pathways. Because SG neurons in the dorsal horn are involved in regulating nociception, manipulating neuronal excitability via SK channels indicates a potential therapeutic target.
authors.affiliation: Electrophysiology Laboratory, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Basic Medical Sciences, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China. Electronic address: yangk@ujs.edu.cn.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001030:Apamin / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000502:physiology*; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013376:Substantia Gelatinosa / Q000502:physiology*
chemical_list: D001562:Benzimidazoles; D016194:Receptors, N-Methyl-D-Aspartate; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; C102635:1-ethyl-2-benzimidazolinone
keywords: 1-EBIO; Apamin; Ca(2+)-activated K(+) channels; Pain; Spinal cord