Safiulina Victoria F, Kasyanov Alexander M, Giniatullin Rashid, Cherubini Enrico
Neuroscience Programme, International School for Advanced Studies, Trieste, Italy.
J Neurophysiol. 2005 Oct;94(4):2797-804. doi: 10.1152/jn.00445.2005. Epub 2005 Aug 10.
Adenosine is a widespread neuromodulator that can be directly released in the extracellular space during sustained network activity or can be generated as the breakdown product of adenosine triphosphate (ATP). Whole cell patch-clamp recordings were performed from CA3 principal cells and interneurons in hippocampal slices obtained from P2-P7 neonatal rats to study the modulatory effects of adenosine on giant depolarizing potentials (GDPs) that constitute the hallmark of developmental networks. We found that GDPs were extremely sensitive to the inhibitory action of adenosine (IC(50) = 0.52 microM). Adenosine also contributed to the depressant effect of ATP as indicated by DPCPX-sensitive changes of ATP-induced reduction of GDP frequency. Similarly, adenosine exerted a strong inhibitory action on spontaneous glutamatergic synaptic events recorded from GABAergic interneurons and on interictal bursts that developed in CA3 principal cells after blockade of gamma-aminobutyric acid type A (GABA(A)) receptors with bicuculline. All these effects were prevented by DPCPX, indicating the involvement of inhibitory A1 receptors. In contrast, GABAergic synaptic events were not changed by adenosine. Consistent with the endogenous role of adenosine on network activity, DPCPX per se increased the frequency of GDPs, interictal bursts, and spontaneous glutamatergic synaptic events recorded from GABAergic interneurons. Moreover, the adenosine transport inhibitor NBTI and the adenosine deaminase blocker EHNA decreased the frequency of GDPs, thus providing further evidence that endogenous adenosine exerts a powerful control on GDP generation. We conclude that, in the neonatal rat hippocampus, the inhibitory action of adenosine on GDPs arises from the negative control of glutamatergic, but not GABAergic, inputs.
腺苷是一种广泛存在的神经调质，在持续的网络活动期间可直接释放到细胞外空间，或者作为三磷酸腺苷（ATP）的分解产物生成。采用全细胞膜片钳记录技术，从出生后2 - 7天新生大鼠的海马切片中的CA3主细胞和中间神经元进行记录，以研究腺苷对构成发育网络标志的巨大去极化电位（GDPs）的调节作用。我们发现GDPs对腺苷的抑制作用极其敏感（半数抑制浓度[IC(50)] = 0.52微摩尔）。如DPCPX敏感的ATP诱导的GDP频率降低变化所示，腺苷也促成了ATP的抑制作用。同样，腺苷对从GABA能中间神经元记录到的自发性谷氨酸能突触事件以及用荷包牡丹碱阻断γ-氨基丁酸A型（GABA(A)）受体后在CA3主细胞中出现的发作间期爆发具有强烈的抑制作用。所有这些效应都被DPCPX阻断，表明抑制性A1受体参与其中。相比之下，腺苷对GABA能突触事件没有影响。与腺苷对网络活动的内源性作用一致，DPCPX本身增加了从GABA能中间神经元记录到的GDPs、发作间期爆发和自发性谷氨酸能突触事件的频率。此外，腺苷转运抑制剂NBTI和腺苷脱氨酶阻滞剂EHNA降低了GDPs的频率，从而进一步证明内源性腺苷对GDP生成具有强大的控制作用。我们得出结论，在新生大鼠海马中，腺苷对GDPs的抑制作用源于对谷氨酸能而非GABA能输入的负调控。
