Lockhart S T, Turrigiano G G, Birren S J
Department of Biology, Brandeis University, Waltham, Massachusetts 02254-9110, USA.
J Neurosci. 1997 Dec 15;17(24):9573-82. doi: 10.1523/JNEUROSCI.17-24-09573.1997.
Regulation of heart rate by the sympathetic nervous system involves the release of norepinephrine (NE) from nerve terminals onto heart tissue, resulting in an elevation in beat rate. Nerve growth factor (NGF) is a neurotrophin produced by the heart that supports the survival and differentiation of sympathetic neurons. Here we report that NGF also functions as a modulator of sympathetic synaptic transmission. We determined the effect of NGF on the strength of synaptic transmission in co-cultures of neonatal rat cardiac myocytes and sympathetic neurons from the superior cervical ganglion (SCG). Synaptic transmission was assayed functionally, as an increase in the beat rate of a cardiac myocyte during stimulation of a connected neuron. Application of NGF produced a pronounced, reversible enhancement of synaptic strength. We found that TrkA, the receptor tyrosine kinase that mediates many NGF responses, is expressed primarily by neurons in these cultures, suggesting a presynaptic mechanism for the effects of NGF. A presynaptic model is further supported by the finding that NGF did not alter the response of myocytes to application of NE. In addition to the acute modulatory effects of NGF, we found that the concentration of NGF in the growth medium affects the level of synaptic transmission in cultures of sympathetic neurons and cardiac myocytes. These results indicate that in addition to its role as a survival factor, NGF plays both acute and long-term roles in the regulation of developing sympathetic synapses in the cardiac system.
交感神经系统对心率的调节涉及神经末梢向心脏组织释放去甲肾上腺素（NE），从而导致心率升高。神经生长因子（NGF）是心脏产生的一种神经营养因子，可支持交感神经元的存活和分化。在此我们报告，NGF还作为交感神经突触传递的调节剂发挥作用。我们确定了NGF对新生大鼠心肌细胞与颈上神经节（SCG）交感神经元共培养物中突触传递强度的影响。通过在刺激相连神经元时心肌细胞的心率增加来功能性地测定突触传递。应用NGF可使突触强度显著且可逆地增强。我们发现，介导许多NGF反应的受体酪氨酸激酶TrkA主要由这些培养物中的神经元表达，这表明NGF的作用存在一种突触前机制。NGF不会改变心肌细胞对NE应用的反应这一发现进一步支持了突触前模型。除了NGF的急性调节作用外，我们还发现生长培养基中NGF的浓度会影响交感神经元和心肌细胞培养物中的突触传递水平。这些结果表明，NGF除了作为一种存活因子发挥作用外，在心脏系统中发育中的交感突触调节中还发挥着急性和长期作用。
