title: Adenosine release mediates cyanide-induced suppression of CA1 neuronal activity.
abstract: The rapid suppression of CNS function produced by cyanide (CN) was studied by field, intracellular, and whole-cell recording in hippocampal slices (at 33-34 degrees C). Population spikes and field EPSPs were depressed by 4-5 min bath applications of 50-100 microM CN (IC50 was 18 miroM for spikes and 72 microM for EPSPs). The actions of CN were reversibly suppressed by the adenosine antagonists 8-sulfophenyltheophylline (8-SPT; 10 microM) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.2 microM), potentiated by the adenosine transport inhibitor dipyridamole (0.5 microM), but unaffected by the KATP channel blocker glyburide (10 microM). Therefore the CN-induced reductions of synaptic efficacy and postsynaptic excitability-demonstrated by synaptic input:output plots-are mediated mainly by adenosine. In whole-cell or intracellular recordings, CN depressed EPSCs and elicited an increase in input conductance and an outward current, the reversal potential of which was approximately -90 mV (indicating that K+ was the major carrier). These effects also were attenuated by 8-SPT. In the presence of 1 mM Ba, CN had no significant postsynaptic action; Cs (2 mM) also prevented CN-induced outward currents but only partly blocked the increase in conductance. Another 8-SPT-sensitive action of CN was to depress hyperpolarization-activated slow inward relaxations (Q current). At room temperature (22-24 degrees C), although it did not change holding current and slow inward relaxations, CN raised the input conductance; this effect also was prevented by 8-SPT (10 microM), but not by glyburide (10 microM). Adenosine release thus appears to be the major link between acute CN poisoning and early depression of CNS synaptic function.
authors.affiliation: Anesthesia Research and Physiology Departments, McGill University, Montréal, Québec, Canada H3G 1Y6.
authors.forename: P J
authors.initials: PJ
authors.lastname: Zhu
authors.forename: K
authors.initials: K
authors.lastname: Krnjević
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D004176:Dipyridamole / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011190:Potassium Cyanide / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D004176:Dipyridamole; C031433:8-(4-sulfophenyl)theophylline; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; D000241:Adenosine; D011190:Potassium Cyanide; D005905:Glyburide