Kappa-Bungarotoxin, a novel neurotoxin, has been purified from snake venom. Kappa-Bungarotoxin belongs to a class of toxins referred to as Alpha-neurotoxins, which are excellent ligands for identifying and characterizing nicotinic cholinergic receptors from skeletal muscle and muscle-derived tissues. Kappa-Bungarotoxin is an unusual Alpha-neurotoxin in that it is physiologically active in a number of neuronal preparations where other Alpha-neurotoxins are ineffective. Neuronal nicotinic transmission is blocked by Kappa-Bungarotoxin at a dose of 40-150 nM. In this proposal, Kappa-Bungarotoxin will be used to identify and characterize the neuronal nicotinic receptor. Experiments already done using radiolabeled Kappa-Bungarotoxin indicate that the toxin binds to at least two sites in neuronal tissue, only one of which may be the physiologically relevant nicotinic receptor. Further experiments will characterize the binding of radiolabeled Kappa-Bungarotoxin in several neuronal systems, including autonomic ganglia and the central nervous systems of the chick and rat. Electrophysiological experiments will be carried out in these preparations so as to directly compare blockade of function of nicotinic receptors with the binding data. Finally, an antomical study will be done to determine the ultrastructural localization of the receptors. It is hoped that these experiments will provide a new understanding of the neuronal nicotinic receptor. This is the first study in which the electrophysiology, biochemistry and morphology of these receptors will be examined using a single ligand in a well-defined model system, the chick ciliary ganglion. Several disease states involve alterations in neuronal cholinergic function. A marked decrease in cholinergic transmission has been observed in patients suffering from Alzheimer's disease. In certain forms of epilepsy, an autoimmune reaction against neuronal nicotinic receptors may occur similar to the attack of the muscle nicotinic receptor seen in patients with myasthenia gravis. By further characterizing cholinergic meurotransmission, the experiments proposed in this study may provide a better understanding of these diseases.
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