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      In vitro hyperglycemia enhances sodium currents in dorsal root ganglion neurons: an effect attenuated by carbamazepine.

      1 , 2 , 2
      Neuroscience
      Elsevier BV

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          Abstract

          Neuropathy is often seen in uncontrolled diabetes and the mechanisms involved for neuropathic pain are poorly understood. Hyperglycemia is a consequence of chronic uncontrolled diabetes and it is postulated to produce neuropathic pain. Therefore, in this study, we have investigated the effects of hyperglycemia on Na(+) channel kinetics in cultured dorsal root ganglion (DRG) neurons from neonatal rats using whole-cell patch-clamp technique. Hyperglycemia-induced increase in density of tetrodotoxin resistant (TTXr) Na(+) currents was increased in time- and concentration-dependent manner. The increase was maximal with 60 mM and 24 h. There was no change Na(+) current density in time-matched control neurons. The conductance curve of TTXr Na(+) current shifted leftward after 24 h exposure to 45 mM glucose. Carbamazepine (CBZ, 100 μM) depressed TTXr Na(+) current in neurons incubated with control (17.26), 45 and 60 mM of glucose. The depression observed with CBZ in the presence of high glucose, i.e., 45 mM (86.5±4.9%) was significantly greater than control (61.6±1.8%). Hyperglycemia also increased reactive oxygen species (ROS) activity and was attenuated by CBZ. These results suggest that short-term exposure of DRG neurons to high glucose concentrations enhance the Na(+) channel activity, and were attenuated by CBZ via ROS-dependent mechanisms.

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          Author and article information

          Journal
          Neuroscience
          Neuroscience
          Elsevier BV
          1873-7544
          0306-4522
          Mar 01 2013
          : 232
          Affiliations
          [1 ] Electrophysiology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)(1), S. A. S. Nagar (Mohali) 160 062, Punjab, India. Electronic address: jitnsingh@gmail.com.
          [2 ] Electrophysiology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)(1), S. A. S. Nagar (Mohali) 160 062, Punjab, India.
          Article
          S0306-4522(12)01192-X
          10.1016/j.neuroscience.2012.12.011
          23262239
          d1f3d72c-3b57-45cb-b6d4-ae56a13c29c2
          History

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