International Center of Molecular Physiology of National Academy of Sciences of Ukraine, 4 Bogomoletz Street., Kyiv 01024, Ukraine ; State Key Laboratory of Molecular and Cellular Biology, Bogomoletz Institute of Physiology of National Academy of Sciences of Ukraine, 4 Bogomoletz Street, Kyiv 01024, Ukraine.
State Key Laboratory of Molecular and Cellular Biology, Bogomoletz Institute of Physiology of National Academy of Sciences of Ukraine, 4 Bogomoletz Street, Kyiv 01024, Ukraine.
Neural Plast. 2014;2014:938235. doi: 10.1155/2014/938235. Epub 2014 Feb 18.
T-type Ca²⁺ channels are known as important participants of nociception and their remodeling contributes to diabetes-induced alterations of pain sensation. In this work we have established that about 30% of rat nonpeptidergic thermal C-type nociceptive (NTCN) neurons of segments L4-L6 express a slow T-type Ca²⁺ current (T-current) while a fast T-current is expressed in the other 70% of these neurons. Streptozotocin-induced diabetes in young rats resulted in thermal hyperalgesia, hypoalgesia, or normalgesia 5-6 weeks after the induction. Our results show that NTCN neurons obtained from hyperalgesic animals do not express the slow T-current. Meanwhile, the fraction of neurons expressing the slow T-current did not significantly change in the hypo- and normalgesic diabetic groups. Moreover, the peak current density of fast T-current was significantly increased only in the neurons of hyperalgesic group. In contrast, the peak current density of slow T-current was significantly decreased in the hypo- and normalgesic groups. Experimental diabetes also resulted in a depolarizing shift of steady-state inactivation of fast T-current in the hyperalgesic group and slow T-current in the hypo- and normalgesic groups. We suggest that the observed changes may contribute to expression of different types of peripheral diabetic neuropathy occurring during the development of diabetes mellitus.
T 型钙通道被认为是伤害感受的重要参与者,其重塑有助于糖尿病引起的疼痛感觉改变。在这项工作中,我们已经确定,大约 30%的 L4-L6 节段大鼠非肽类热敏 C 型伤害感受神经元(NTCN)表达一种缓慢的 T 型钙电流(T 电流),而另 70%的这些神经元表达快速 T 电流。链脲佐菌素诱导的年轻大鼠糖尿病在诱导后 5-6 周导致热痛觉过敏、痛觉减退或正常痛觉。我们的结果表明,来自痛觉过敏动物的 NTCN 神经元不表达慢 T 电流。同时,在痛觉减退和正常痛觉糖尿病组中,表达慢 T 电流的神经元比例没有显著变化。此外,仅在痛觉过敏组的神经元中,快速 T 电流的峰值电流密度显著增加。相比之下,在痛觉减退和正常痛觉组中,慢 T 电流的峰值电流密度显著降低。实验性糖尿病也导致快速 T 电流的稳态失活和痛觉减退以及正常痛觉组的慢 T 电流的去极化偏移。我们认为,观察到的变化可能有助于表达糖尿病发生过程中发生的不同类型的周围性糖尿病神经病变。