strychnine and Ischemia

An ischemia-induced change in glutamatergic transmission was investigated in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by use of the whole cell patch-clamp technique; the ischemia was simulated by superfusing an oxygen- and glucose-free medium (ISM). Following ISM superfusion, 21 of 37 SG neurons tested produced an outward current (23 +/- 4 pA at a holding potential of -70 mV), which was followed by a slow and subsequent rapid inward current; the remaining neurons had only inward currents. During such a change in holding currents, spontaneous excitatory postsynaptic currents (EPSCs) were remarkably decreased in a frequency with time (half-decay time of the frequency: about 65 s). The frequency of spontaneous EPSCs was reduced to 28 +/- 13% (n = 37) of the control level during the generation of the slow inward current (about 4 min after the beginning of ISM superfusion) without a change in the amplitude of spontaneous EPSCs. When ISM was superfused together with either bicuculline (10 microM) or CGP35348 (20 microM; GABA(A) and GABA(B) receptor antagonists, respectively), spontaneous EPSC frequency reduced by ISM recovered to the control level and then the frequency markedly increased [by 325 +/- 120% (n = 22) and 326 +/- 91% (n = 17), respectively, 4 min after ISM superfusion]; this alteration in the frequency was not accompanied by a change in spontaneous EPSC amplitude. Superfusing TTX (1 microM)-containing ISM resulted in a similar recovery of spontaneous EPSC frequency and following increase (by 328 +/- 26%, n = 12) in the frequency; strychnine (1 microM) did not affect ISM-induced changes in spontaneous EPSC frequency (n = 5). It is concluded that the ischemic simulation inhibits excitatory transmission to SG neurons, whose action is in part mediated by the activation of presynaptic GABA(A) and GABA(B) receptors, probably due to GABA released from interneurons as a result of an ischemia-induced increase in neuronal activities. This action might protect SG neurons from an excessive excitation mediated by L-glutamate during ischemia.

Topics: Age Factors; Anesthetics, Local; Animals; Bicuculline; Excitatory Postsynaptic Potentials; GABA Antagonists; gamma-Aminobutyric Acid; Glutamic Acid; Glycine; Glycine Agents; Ischemia; Male; Neural Inhibition; Organ Culture Techniques; Patch-Clamp Techniques; Rats; Strychnine; Substantia Gelatinosa; Tetrodotoxin

The 'switching model' for generation of respiratory rhythms holds that gasping represents the release of a rostral medullary pacemaker mechanism from the pontomedullary neuronal circuit that generates eupnea. In a perfused preparation of the decerebrate juvenile rat, exposure to ischemia or hypoxic-hypercapnia caused an alteration in integrated phrenic activity from the incrementing pattern of eupnea to the decrementing pattern of gasping. The time required to elicit gasping was not altered by multiple exposures to ischemia or hypoxic-hypercapnia. Furthermore, this time to gasping was not altered following addition to the perfusate of increasing concentrations of bicuculline or picrotoxin; both block GABA(A) receptors. Addition to the perfusate of strychnine, a glycine antagonist, significantly shortened the duration of ischemia or hypoxic-hypercapnia required to elicit gasping. These results support the concept that a loss of inhibitory glycinergic transmission is a critical factor in release of pacemaker mechanisms for gasping from the pontomedullary neuronal circuit for eupnea.

Topics: Animals; GABA-A Receptor Antagonists; Hypercapnia; Hypoxia; In Vitro Techniques; Ischemia; Rats; Receptors, GABA-A; Receptors, Glycine; Respiration; Strychnine

Topics: Animals; Brain; Cerebral Cortex; Cerebrovascular Disorders; Dogs; Electroencephalography; Ischemia; Seizures; Strychnine

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Anaerobiosis; Animals; Brain; Brain Chemistry; Cerebral Cortex; Cerebrovascular Circulation; Cerebrovascular Disorders; Dogs; Electroencephalography; Evoked Potentials; Glycolysis; Ischemia; Perfusion; Strychnine

Topics: Animals; Cats; Cerebral Cortex; Electric Stimulation; Extremities; Ischemia; Medulla Oblongata; Mesencephalon; Peripheral Nerves; Reticular Formation; Retina; Spinal Cord; Strychnine

Topics: Animals; Barbiturates; Cats; Ischemia; Light; Optic Nerve; Retinal Vessels; Strychnine

Topics: Aminobutyrates; Carotid Arteries; Cerebral Cortex; Chromatography; Citric Acid Cycle; Depression; Electroencephalography; gamma-Aminobutyric Acid; Ischemia; Lactates; Physiology; Potassium; Pyruvates; Rats; Research; Solutions; Strychnine

Topics: Carotid Arteries; Cerebral Cortex; Citrates; Citric Acid Cycle; Depression; Electroencephalography; Glucose; Glycogen; Ischemia; Ketoglutaric Acids; Lactates; Pharmacology; Physiology; Potassium; Pyruvates; Rats; Research; Sodium Chloride; Strychnine