Sun B B, Chiu S Y
Graduate Program in Biophysics, University of Wisconsin School of Medicine, Madison, Wisconsin 53706, USA.
J Neurosci. 1999 Jul 1;19(13):5185-94. doi: 10.1523/JNEUROSCI.19-13-05185.1999.
Axons of neonatal rat optic nerves exhibit fast calcium transients in response to brief action potential stimulation. In response to one to four closely spaced action potentials, evoked calcium transients showed a fast-rising phase followed by a decay with a time constant of approximately 2-3 sec. By selective staining of axons or glial cells with calcium dyes, it was shown that the evoked calcium transient originated from axons. The calcium transient was caused by influx because it was eliminated when bath calcium was removed. Pharmacological profile studies with calcium channel subtype-specific peptides suggested that 58% of the evoked calcium influx was accounted for by N-type calcium channels, whereas L- and P/Q-type calcium channels had little, if any, contribution. The identity of the residual calcium influx remains unclear. GABA application caused a dramatic reduction of the amplitude of the action potential and the associated calcium influx. When GABAA receptors were blocked by bicuculline, the inhibitory effect of GABA on the action potential was eliminated, whereas that on the calcium influx was not, indicating involvement of GABAB receptors. Indeed, the calcium influx was inhibited by the GABAB receptor agonist baclofen. This baclofen effect was occluded by a previous block of N-type calcium channels and was unaffected by the broad-spectrum K+ channel blocker 4-AP. We conclude that neonatal rat optic nerve axons express N-type calcium channels, which are subjected to regulation by G-protein-coupled GABAB receptors. We suggest that receptor-mediated inhibition of axonal calcium channels plays a protective role in neonatal anoxic and/or ischemic injury.
新生大鼠视神经轴突在受到短暂动作电位刺激时会表现出快速钙瞬变。在对一到四个紧密间隔的动作电位做出反应时，诱发的钙瞬变呈现出快速上升阶段，随后以大约2 - 3秒的时间常数衰减。通过用钙染料对轴突或神经胶质细胞进行选择性染色，结果表明诱发的钙瞬变起源于轴突。钙瞬变是由钙内流引起的，因为去除浴液中的钙时它就会消失。用钙通道亚型特异性肽进行的药理学特性研究表明，诱发的钙内流中有58%是由N型钙通道介导的，而L型和P/Q型钙通道即使有贡献也很小。剩余钙内流的身份尚不清楚。应用γ-氨基丁酸（GABA）会导致动作电位幅度和相关钙内流显著降低。当用荷包牡丹碱阻断GABAA受体时，GABA对动作电位的抑制作用消失，而对钙内流的抑制作用并未消失，这表明GABAB受体参与其中。事实上，GABAB受体激动剂巴氯芬抑制了钙内流。这种巴氯芬效应在先前阻断N型钙通道后被抵消，并且不受广谱钾通道阻滞剂4-氨基吡啶（4-AP）的影响。我们得出结论，新生大鼠视神经轴突表达N型钙通道，这些通道受到G蛋白偶联的GABAB受体的调节。我们认为受体介导的轴突钙通道抑制在新生儿缺氧和/或缺血性损伤中起保护作用。
