Sodium channel expression in hypothalamic osmosensitive neurons in experimental diabetes.
Vasopressin is synthesized by neurons in the supraoptic nucleus of the hypothalamus and its release is controlled by action potentials produced by specific subtypes of voltage-gated sodium channels expressed in these neurons. The hyperosmotic state associated with uncontrolled diabetes mellitus causes elevated levels of plasma vasopressin, which are thought to contribute to the pathologic changes of diabetic nephropathy. We demonstrate here that in the rodent streptozotocin model of diabetes there are increases in expression of mRNA and protein for two sodium channel alpha-subunits and two beta-subunits in the neurons of the supraoptic nucleus. Transient and persistent sodium currents show parallel increases in these diabetic neurons. In the setting of chronic uncontrolled diabetes, these changes in sodium channel expression in the supraoptic nucleus may be maladaptive, contributing to the development of secondary renal complications.
Klein
Joshua P
JP
Department of Neurology and PVA/EPVA Center for Neuroscience and Regeneration Research, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Craner
Matthew J
MJ
Cummins
Theodore R
TR
Black
Joel A
JA
Waxman
Stephen G
SG
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics; D013495:Supraoptic Nucleus / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology*
D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C568253:Scn2A protein, rat; D015222:Sodium Channels