aconitine and Hypoxia

Topics: Aconitine; Action Potentials; Animals; Arrhythmias, Cardiac; Dogs; Electric Stimulation; Hypoxia; Lactates; Muscles; Myocardium; Oscillometry; Purkinje Fibers; Time Factors; Ventricular Fibrillation

The hippocampal interneurons are very diverse by chemical profiles and rather inconsistent by sensitivity to CI. Some hippocampal GABAergic interneurons survive certain time after ischemia while ischemia-sensitive interneurons and pyramidal neurons are damaged. GABAergic signaling, nicotinic receptors expressing α7-subunit (α7nAChRs(+)) and connexin-36 (Cx36(+), electrotonic gapjunctions protein) contradictory modulate post-ischemic environment. We hypothesized that hippocampal ischemia-resistant GABAergic interneurons coexpressing glutamate decarboxylase-67 isoform (GAD67(+)), α7nAChRs(+), Cx36(+) are able to enhance neuronal viability. To check this hypothesis the histochemical and electrophysiological investigations have been performed using rat hippocampal organotypic culture in the condition of 30-min oxygen-glucose deprivation (OGD). Post-OGD reoxygenation (4h) revealed in CA1 pyramidal layer numerous damaged cells, decreased population spike amplitude and increased pair-pulse depression. In these conditions GAD67(+) interneurons displayed the OGD-resistance and significant increase of GABA synthesis/metabolism (GAD67-immunofluorescence, mitochondrial activity). The α7nAChRs(+) and Cx36(+) co-localizations were revealed in resistant GAD67(+) interneurons. Under OGD: GABAA-receptors (GABAARs) blockade increased cell damage and exacerbated the pair-pulse depression in CA1 pyramidal layer; α7nAChRs and Cx36-channels separate blockades sufficiently decreased cell damage while interneuronal GAD67-immunofluorescence and mitochondrial activity were similar to the control. Thus, hippocampal GABAergic interneurons co-expressing α7nAChRs and Cx36 remained resistant certain time after OGD and were able to modulate CA1 neuron survival through GABAARs, α7nAChRs and Cx36-channels activity. The enhancements of the neuronal viability together with GABA synthesis/metabolism normalization suggest cooperative neuroprotective mechanism that could be used for increase in efficiency of therapeutic strategies against post-ischemic pathology.

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Animals, Newborn; Carbenoxolone; Connexins; GABA Antagonists; gamma-Aminobutyric Acid; Gap Junction delta-2 Protein; Gene Expression Regulation; Glucose; Glutamate Decarboxylase; Hippocampus; Hypoxia; In Vitro Techniques; Interneurons; Mefloquine; Mitochondria; Nicotinic Antagonists; Organ Culture Techniques; Patch-Clamp Techniques; Pyridazines; Rats; Rats, Wistar; Synaptic Transmission

Hypobaric hypoxic preconditioning increased the resistance of low resistant and highly resistant rats to acute hypobaric hypoxia at a critical height. Intergroup differences in the resistance of rats to acute hypobaric hypoxia were not observed after hypobaric hypoxia and one variational series with a wide range of resistance (4.5-24.5 min) appeared. Methyllycaconitine, an antagonist of subtype α(7) nicotinic cholinergic receptors, abolished the influence of hypobaric hypoxia on low resistant rats, but had no effect on highly resistant animals. Mecamylamine, a preferential antagonist of subtype α(4)β(2) and α(3)-containing cholinergic receptors, did not modulate the effect of hypobaric hypoxia. By contrast, hypobaric hypoxia abolished the effect of mecamylamine on the resistance of rats that were not trained under conditions of hypobaric hypoxia (low resistant and highly resistant animals with low sensitivity to hypobaric hypoxia). We conclude that the same effect of hypobaric hypoxia is mediated by various mechanisms, which involve different nicotinic cholinergic receptors. They differ from the resistance mechanisms in non-trained rats.

Topics: Aconitine; Adaptation, Physiological; Air Pressure; Animals; Asphyxia; Hypoxia; Male; Mecamylamine; Nicotinic Antagonists; Rats; Receptors, Nicotinic

The method for inducing arrhythmias or asystole by the application of a 50 Hz alternating current (ac) has been applied to isolated guinea-pig left atria and papillary muscles in order to characterize arrhythmogenic and antiarrhythmic substances. Aconitine, BaCl2 (less than 2 mmol/l) and hypoxia decrease threshold of ac-arrhythmia and ac-asystole, in both tissues to a similar extent, whereas carbachol and BaCl2 (greater than 2 mmol/l) increase threshold. The calcium antagonists nifedipine and diltiazem lower threshold of ac-asystole but differ with respect to threshold of ac-arrhythmia, which is increased by 10(-6) mol/l diltiazem in left atria and papillary muscles by about 30% and remains nearly unaffected with nifedipine. The Na+-inhibitory substance flecainide reverses the decrease in threshold of ac-arrhythmia and ac-asystole brought about by aconitine. Threshold of ac-arrhythmia lowered by hypoxia is increased by diltiazem in a concentration-dependent manner, whereas decrease of threshold of ac-asystole is even augmented. Therefore, the method offers an opportunity of quantifying the action of arrhythmogenic agents at concentrations which are too low to induce arrhythmia, as well as to characterize the activity of antiarrhythmic drugs in the presence of arrhythmogenic substances.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Barium; Barium Compounds; Calcium Channel Blockers; Carbachol; Chlorides; Electric Stimulation; Guinea Pigs; Heart Atria; Hypoxia; In Vitro Techniques; Isoproterenol; Male; Papillary Muscles; Receptors, Cholinergic