INTRINSIC CARDIAC NEURONS AND CARDIAC CONTROL

描述(改编自申请人的摘要)：申请人提出 探讨心内神经的生理学意义 系统。申请者的主要目标是确定具体的 心脏固有神经节和心肌细胞内的缺陷 受体-效应器突触连接发生在 心脏分散和/或肾上腺切除术。为此目的，五 已经确定了具体的目标。具体目标1.确定是否延长了 失去心脏的外源性神经输入和/或失去肾上腺髓质 支持改变基础神经活动和突触内的相互作用 在体心内神经节对应用特异性药物的反应 胆碱能和非胆碱能激动剂和拮抗剂。具体目标2. 以确定心脏和/或外源性神经输入的长期丢失 肾上腺髓质支持的丧失改变了膜的特性和 心脏神经元的突触效能。利用细胞内微电极 体外整体贴装心内神经节、体细胞技术的应用 对特定胆碱能和非胆碱能激动剂的反应和 拮抗剂将在电刺激之前和期间进行评估。 神经节间神经。具体目标3.使用受体放射自显影，以 确定心脏和/或心脏的外源性神经输入是否长期丢失 肾上腺髓质支持的长期丧失会改变特定的胆碱能， 肾上腺素能和血管紧张素II受体的密度和分布 心内神经节或在电和收缩内 狗心脏的组织。具体目标4.确定是否延长了 失去心脏的外源性神经输入和/或长期失去肾上腺 髓质支持改变心肌细胞内的信号转导。 具体目标5.确定循环儿茶酚胺的恢复 缓解慢性肾上腺切除所致的心脏抑制 而不会同时延长外周神经输入的丢失 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.