1 Department of Anesthesiology and Perioperative Medicine, College of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Mol Pain. 2018 Jan-Dec;14:1744806918814350. doi: 10.1177/1744806918814350. Epub 2018 Oct 31.
Cooling temperatures and low pH have profound effects on somatosensory functions including nociception. The effects not only can be mediated by cooling temperature transducers and proton transducers expressed in subpopulations of somatosensory neurons but may also be mediated by ion channels involving membrane excitability such as voltage-dependent K channels in somatosensory neurons. In the present study, we performed the in situ patch-clamp recordings from nociceptive-like trigeminal ganglion neurons in ex vivo trigeminal ganglion preparations of adult rats. We determined effects of cooling temperatures and low pH on membrane properties and voltage-dependent currents in nociceptive-like trigeminal ganglion neurons. Action potential rheobase levels were decreased when nociceptive trigeminal ganglion neurons were cooled from 24°C down to 12°C or when extracellular pH levels were reduced from 7.3 to 6. This indicates that the excitability of nociceptive-like trigeminal ganglion neurons was increased at the cooling temperatures and low pH. The decreases of action potential rheobase levels were accompanied by increases of trigeminal ganglion neuron input resistances at cooling temperatures and low pH, suggesting a possible involvement of background K channels. Cooling temperatures and low pH suppressed voltage-activated inward Na currents and also voltage-dependent outward K currents in nociceptive-like trigeminal ganglion neurons. Voltage-dependent outward K currents in nociceptive-like trigeminal ganglion neurons consist of inactivating A-type K currents and non-inactivating type K currents, and the former were more sensitive to cooling temperatures and low pH. Collectively, suppressing multiple types of K channels may be associated with the enhanced excitability of nociceptive trigeminal ganglion neurons by cooling temperatures and low pH.
冷却温度和低 pH 值对包括伤害感受在内的躯体感觉功能有深远影响。这些影响不仅可以通过在躯体感觉神经元的亚群中表达的冷却温度传感器和质子传感器来介导，还可以通过涉及膜兴奋性的离子通道来介导，如躯体感觉神经元中的电压依赖性 K 通道。在本研究中，我们对成年大鼠离体三叉神经节标本中的伤害感受样三叉神经节神经元进行了原位膜片钳记录。我们确定了冷却温度和低 pH 值对伤害感受样三叉神经节神经元膜特性和电压依赖性电流的影响。当伤害感受性三叉神经节神经元从 24°C 冷却至 12°C 或细胞外 pH 值从 7.3 降低至 6.0 时，动作电位基强度降低。这表明在冷却温度和低 pH 值下，伤害感受样三叉神经节神经元的兴奋性增加。动作电位基强度的降低伴随着在冷却温度和低 pH 值下三叉神经节神经元输入电阻的增加，这表明背景 K 通道可能参与其中。冷却温度和低 pH 值抑制伤害感受样三叉神经节神经元中的电压激活内向 Na 电流和电压依赖性外向 K 电流。伤害感受样三叉神经节神经元中的电压依赖性外向 K 电流由失活 A 型 K 电流和非失活 K 电流组成，前者对冷却温度和低 pH 值更为敏感。总的来说，抑制多种类型的 K 通道可能与冷却温度和低 pH 值增强伤害感受三叉神经节神经元的兴奋性有关。
