Effects of ion gradients on the release of neurotransmitter from autonomic nerve endings in vivo.

1)为了探讨缺氧对心脏交感神经末梢内源性去甲肾上腺素（NE）释放的影响，我们通过透析探针向心肌间隙注入氰化钠（NaCN） 30 min，测量透析液NE水平。在NaCN灌注期间，观察到透析液NE的显著浓度依赖性增加。这种氰化物诱导的NE反应被去吡拉明（一种膜性NE运输抑制剂）预处理抑制。此外，TMB-8（胞内Ca^<2+>拮抗剂）预处理可抑制氰化物诱导的NE反应，但ω- concontoxin GVIA （NE释放抑制剂）对其无影响。我们的数据表明，两个独立的机制（地西帕明或TMB-8抑制）促成了氰化物在体内心脏交感神经中诱导的NE外排量。2)冠状动脉闭塞引起的急性心肌缺血使缺血区心肌间质乙酰胆碱（ACh）和NE水平升高，非缺血区心肌间质乙酰胆碱（ACh）水平升高，NE水平降低。缺血区乙酰胆碱释放主要归因于局部释放机制，而非缺血区乙酰胆碱释放则依赖于迷走传出神经活动的增加。局部释放机制依赖于细胞内Ca^<2+>的动员，而不依赖于n型Ca^<2+>通道的打开。

1) To investigate the effect of hypoxia on endogenous norepinephrine (NE) release from cardiac sympathetic nerve ending, we administered sodium cyanide (NaCN) for 30 min into the myocardial interstitial space through a dialysis probe and measured dialysate NE levels. During the NaCN perfusion, a marked and concentration-dependent increase in dialysate NE was observed. This cyanide induced NE response was suppressed by pretreatment with despiramine (a membranous NE transport inhibitor). Further, the cyanide induced NE response was suppressed by pretreatment with TMB-8 (intracellular Ca^<2+> antagonist) but unaffected by ω-conotoxin GVIA (NE releasing inhibitor). Our data suggest that two independent (desipramine or TMB-8 suppressive) mechanisms contributed to the amount of NE efflux induced by cyanide in in vivo cardiac sympathetic nerve.2) Acute myocardial ischemia induced by coronary occlusion increased myocardial interstitial acetylcholine (ACh) and NE levels in ischemic region, whereas, in non-ischemic region, coronary occlusion increased myocardial ACh level but decreased the NE level. The ACh release in the ischemic region is mainly attributed to local release mechanism, whereas the ACh release in the non-ischemic region depends on the increased vagal efferent nerve activity. The local release mechanism would depend on intracellular Ca^<2+> mobilization but not on N-type Ca^<2+> channel opening.