Effect of NaCN on currents evoked by uremic retention solutes in dissociated mouse neurons.
Uremic retention solutes possibly contribute to neuronal hypoxia/ischemia and its consequences in patients with renal failure. We examined the in vitro effects of several uremic retention solutes on murine central neurons under chemically induced metabolic hypoxia by application of sodium cyanide (NaCN). Whole cell currents were recorded using the tight-seal whole-cell voltage clamp technique. Application of NaCN caused an inward whole-cell current. From all tested toxins, which included several indoles, guanidino compounds, polyamines, purines, phenols, DL-homocysteine, orotate and myoinositol, only creatinine (CTN), guanidine (G) and guanidinosuccinic acid (GSA) produced a significant current in control and hypoxic neurons. Current evoked by GSA was significantly increased in the chemical hypoxic condition, and a synergistic effect of GSA and spermine was observed in hypoxic neurons.
Torremans
A
A
Laboratory of Neurochemistry and Behaviour/Born Bunge Foundation, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp (Wilrijk), Belgium.
D'Hooge
R
R
Van de Vijver
G
G
Marescau
B
B
Vanholder
R
R
Lameire
N
N
De Deyn
P P
PP
Van Bogaert
P P
PP
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology; D003404:Creatinine / Q000494:pharmacology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000633:toxicity*; D019791:Guanidine / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000378:metabolism* / Q000633:toxicity; D018408:Patch-Clamp Techniques / Q000379:methods; D012966:Sodium Cyanide / Q000633:toxicity*; D013386:Succinates / Q000494:pharmacology; D014511:Uremia / Q000378:metabolism*
D004791:Enzyme Inhibitors; D006146:Guanidines; D009498:Neurotoxins; D013386:Succinates; D001224:Aspartic Acid; C001318:guanidinosuccinic acid; D003404:Creatinine; D019791:Guanidine; D012966:Sodium Cyanide