Graham B A, Brichta A M, Schofield P R, Callister R J
School of Biomedical Sciences, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia.
J Physiol. 2007 Oct 1;584(Pt 1):121-36. doi: 10.1113/jphysiol.2007.138198. Epub 2007 Aug 9.
The spastic mouse has a naturally occurring glycine receptor (GlyR) mutation that disrupts synaptic input in both motor and sensory pathways. Here we use the spastic mouse to examine how this altered inhibitory drive affects neuronal intrinsic membrane properties and signal processing in the superficial dorsal horn (SDH), where GlyRs contribute to pain processing mechanisms. We first used in vitro patch clamp recording in spinal cord slices (L3-L5 segments) to examine intrinsic membrane properties of SDH neurones in spastic and age-matched wildtype controls ( approximately P23). Apart from a modest reduction ( approximately 3 mV) in resting membrane potential (RMP), neurones in spastic mice have membrane and action potential (AP) properties identical to wildtype controls. There was, however, a substantial reorganization of AP discharge properties in neurones from spastic mice, with a significant increase (14%) in the proportion of delayed firing neurones. This was accompanied by a change in the voltage sensitivity of rapid A-currents, a possible mechanism for increased delayed firing. To assess the functional consequences of these changes, we made in vivo patch-clamp recordings from SDH neurones in urethane anaesthetized (2.2 g kg(-1), i.p.) spastic and wildtype mice ( approximately P37), and examined responses to innocuous and noxious mechanical stimulation of the hindpaw. Overall, responses recorded in wildtype and spastic mice were similar; however, in spastic mice a small population of spontaneously active neurones ( approximately 10%) exhibited elevated spontaneous discharge frequency and post-pinch discharge rates. Together, these results are consistent with the altered intrinsic membrane properties of SDH neurones observed in vitro having functional consequences for pain processing mechanisms in the spastic mouse in vivo. We propose that alterations in potassium channel function in the spastic mouse compensate, in part, for reduced glycinergic inhibition and thus maintain normal signal processing in the SDH.
痉挛小鼠存在一种自然发生的甘氨酸受体（GlyR）突变，该突变会破坏运动和感觉通路中的突触输入。在此，我们利用痉挛小鼠来研究这种改变的抑制性驱动如何影响浅表背角（SDH）中神经元的内在膜特性和信号处理，在该区域甘氨酸受体参与疼痛处理机制。我们首先在脊髓切片（L3 - L5节段）中使用体外膜片钳记录来检查痉挛小鼠和年龄匹配的野生型对照（约P23）中SDH神经元的内在膜特性。除了静息膜电位（RMP）有适度降低（约3 mV）外，痉挛小鼠中的神经元具有与野生型对照相同的膜和动作电位（AP）特性。然而，痉挛小鼠神经元的AP放电特性发生了显著重组，延迟放电神经元的比例显著增加（14%）。这伴随着快速A电流电压敏感性的变化，这可能是延迟放电增加的一种机制。为了评估这些变化的功能后果，我们在乌拉坦麻醉（2.2 g kg⁻¹，腹腔注射）的痉挛小鼠和野生型小鼠（约P37）中对SDH神经元进行体内膜片钳记录，并检查后爪对无害和有害机械刺激的反应。总体而言，野生型和痉挛小鼠中记录到的反应相似；然而，在痉挛小鼠中，一小部分自发活动的神经元（约10%）表现出自发放电频率和捏后放电率升高。总之，这些结果与体外观察到的SDH神经元内在膜特性改变对痉挛小鼠体内疼痛处理机制具有功能后果相一致。我们提出，痉挛小鼠中钾通道功能的改变部分补偿了甘氨酸能抑制的降低，从而维持了SDH中的正常信号处理。
