INTRINSIC CARDIAC NEURONS AND CARDIAC CONTROL

描述（改编自申请人摘要）：申请人提出 研究心脏固有神经的生理学意义 系统 申请人的主要目标是确定具体的 心内神经节和肌细胞内的缺陷 受体-效应器突触连接，发生在 心脏分散和/或肾上腺切除术。 为此，五 已经确定了具体目标。 具体目标1。 以确定是否延长 心脏的外源性神经输入丧失和/或肾上腺髓质功能丧失 支持改变基底神经活动和突触内的相互作用， 体内心内神经节对特异性 胆碱能和非胆碱能激动剂和拮抗剂。 具体目标2。 为了确定是否长期失去心脏的外源性神经输入和/或 肾上腺髓质支持的丧失改变了膜的性质， 心脏神经元的突触功效。 使用细胞内微电极 应用于体外整体安装心内神经节的技术，体细胞 对特异性胆碱能和非胆碱能激动剂的反应， 拮抗剂将在电刺激之前和期间进行评价， 神经节间神经 具体目标3。 使用受体放射自显影术， 确定是否长期丧失心脏的外源性神经输入和/或 肾上腺髓质支持的长期丧失改变了特异性胆碱能， 肾上腺素能和血管紧张素II受体密度和分布 心内神经节或电和收缩神经节内 犬的心脏组织 具体目标4。 以确定是否延长 心脏的外源性神经输入丧失和/或肾上腺皮质功能长期丧失 髓质支持改变心肌细胞内的信号转导。 具体目标5. 为了确定循环中的儿茶酚胺的恢复 证实了慢性肾上腺切除术相关的心脏抑制， 并且没有同时延长的对所述神经系统的外部神经输入的损失， 心

DESCRIPTION (adapted from the applicant's abstract): The applicant proposes to investigate the physiologic importance of the intrinsic cardiac nervous system. The applicant's principal objective is to identify the specific deficits within the intrinsic cardiac ganglia and at the myocyte receptor-effector synaptic junctions that occur subsequent to decentralization of the heart and/or adrenalectomy. For this purpose five specific aims have been defined. Specific Aim 1. To determine if prolonged loss of extrinsic nerve inputs to the heart and/or loss of adrenal medullary support modifies basal nerve activity and synaptic interactions within the in vivo intrinsic cardiac ganglia in response to application of specific cholinergic and non-cholinergic agonists and antagonists. Specific Aim 2. To determine if prolonged loss of extrinsic nerve inputs to the heart and/or loss of adrenal medullary support alters the membrane properties and synaptic efficacy of cardiac neurons. Using intracellular microelectrode techniques applied to in vitro whole mount intracardiac ganglia, somatic responses to specific cholinergic and non-cholinergic agonists and antagonists will be evaluated prior to and during electrical stimulation of interganglionic nerves. Specific Aim 3. Using receptor autoradiography, to determine if prolonged loss of extrinsic nerve inputs to the heart and/or prolonged loss of adrenal medullary support modifies specific cholinergic, adrenergic and angiotensin II receptor densities and distributions within the intrinsic cardiac ganglia or within the electrical and contractile tissues of the canine heart. Specific Aim 4. To determine if prolonged loss of extrinsic nerve inputs to the heart and/or prolonged loss of adrenal medullary support modifies signal transduction within cardiac myocytes. Specific Aim 5. To determine if restoration of circulating catecholamines alleviates the cardiodepression associated with chronic adrenalectomy with and without concurrent prolonged loss of extrinsic nerve inputs to the heart.