CaィイD12+ィエD1-related abnormality in neuronal nicotinic acetylcholine receptor-mutant mice

点击翻译按钮获取中文摘要

Desensitizing interaction between muscle (M)-and neuronal (N)-types of nicotinic acetylcholine receptors (nAChR) occurs through menthyllycaconitine (MLA)-sensitive slow CaィイD12+ィエD1 mobilization (RAMIC : receptor activity-modulating intracellular calcium) in neuromuscular synapse. To elucidate functional roles of N-nAChR in brain and identify the N-nAChR subunit regulating M-nAChR in neuromuscular synapse, we assessed the intracellular CaィイD12+ィエD1 level by imaging fura-2-loaded cells in brain slices (substantia nigra pars compacta) and in single skeletal muscle cells (flexor digitorum brevis) of mice lacking the nAChRβ2-subunit. 1. Neuromuscular synapse : Either RAMIC induced by cytisine (20μM) and Ach (3μM) or desensitization in opening frequency of ACh-activated channel current was observed β2-mutant (-/-) mice in the same manner as in β2(+/+) wildtype sibling mice. 2. Substantia nigra pars compacta : Superfusion with nicotine (10-100μM) caused a long-lasting rise of intracellular CaィイD12+ィエD1 level in an extracellular CaィイD12+ィエD1-dependent manner in wild-type mice but not in β2(-/-) mutant mice. Alpha 7-subunit-selective agonist choline (10mM) caused a MLA-sensitive increase of intracellular CaィイD12+ィエD1 level both in wild-type and β2(-/-) mutant mice. In nigral dopaminergic neurons, nicotine can elicit CaィイD12+ィエD1 mobilization via two distinct mechanisms of either activation of β2- or of α7-subunit-containing nAChR. In neuromuscular synapse, β2-subunit is less involved to produce a MLA-sensitive RAMIC. I