Przywara D A, Mashalkar V, Bhave S V, Wakade T D, Wakade A R
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201.
Eur J Pharmacol. 1993 Nov 15;247(3):353-6. doi: 10.1016/0922-4106(93)90206-o.
A single stimulus applied to sympathetic neurons co-cultured with cardiac cells produced a very small increase in the release of tritiated norepinephrine and intracellular free Ca2+ concentration ([Ca2+]i), but evoked a typical neuronal action potential. Treatment with 10 mM tetraethylammonium caused a dramatic increase in the responses to a single stimulus, and [3H]norepinephrine release remained above baseline for as long as 20 s. [Ca2+]i increased in cell bodies and neurites from basal levels of 50 to 100 nM to over 300 nM. [Ca2+]i remained elevated for 18 +/- 1 s and required 6.8 +/- 0.5 s for 50% recovery to basal levels. Action potential duration at 50% repolarization was increased from 4.5 +/- 0.3 ms to 88 +/- 20 ms and resting membrane potential decreased from -55 +/- 2 to -43 +/- 4 mV in the presence of tetraethylammonium. Repetitive firing was not observed after a single stimulus in current clamped neurons before or during tetraethylammonium exposure. These findings show a direct relation between action potential duration, Ca2+ entry and transmitter release in response to a single stimulus.
对与心脏细胞共培养的交感神经元施加单个刺激,会使氚化去甲肾上腺素的释放和细胞内游离钙离子浓度([Ca2+]i)出现非常小的增加,但会诱发典型的神经元动作电位。用10 mM四乙铵处理会使对单个刺激的反应显著增加,并且[3H]去甲肾上腺素的释放在长达20秒的时间内都保持在基线以上。[Ca2+]i在细胞体和神经突中从50至100 nM的基础水平增加到超过300 nM。[Ca2+]i保持升高18±1秒,恢复到基础水平的50%需要6.8±0.5秒。在存在四乙铵的情况下,50%复极化时的动作电位持续时间从4.5±0.3毫秒增加到88±20毫秒,静息膜电位从-55±2毫伏降低到-43±4毫伏。在四乙铵暴露之前或期间,电流钳制的神经元在单个刺激后未观察到重复放电。这些发现表明,在对单个刺激的反应中,动作电位持续时间、钙离子内流和递质释放之间存在直接关系。