title: In vitro hyperglycemia enhances sodium currents in dorsal root ganglion neurons: an effect attenuated by carbamazepine.
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.
authors.affiliation: 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.
authors.forename: J N
authors.initials: JN
authors.lastname: Singh
authors.affiliation: 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.
authors.forename: G
authors.initials: G
authors.lastname: Jain
authors.affiliation: 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.
authors.forename: S S
authors.initials: SS
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D002220:Carbamazepine / Q000494:pharmacology; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy / Q000503:physiopathology*; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D002220:Carbamazepine; D013779:Tetrodotoxin; D012964:Sodium; D005947:Glucose