Kehoe J
Laboratoire de Neurobiologie, Ecole Normale Supérieure, Paris, France.
J Neurosci. 1990 Oct;10(10):3194-207. doi: 10.1523/JNEUROSCI.10-10-03194.1990.
Cyclic nucleotides have been implicated in many long-lasting transmitter-induced effects on membrane conductance. One previously observed effect of cAMP on molluscan neurons is to induce a slow inward current, which has been further evaluated here in depolarized anterior and medial cells of the pleural ganglion of Aplysia californica in order to understand better its underlying ionic mechanisms and its sensitivity to a variety of pharmacological agents. This current, which appears to be the only cAMP-induced current seen in the anterior cells, was shown to invert at about +25 mV, that is, approximately 25-30 mV inferior to ENa. This reversal potential was lowered by about 15-16 mV when half of the extracellular Na was replaced by either mannitol or N-methyl-D-glucamine, whereas it was unaffected by changes in extracellular Cl, Ca, or Mg. The response persisted in seawater in which the Na had been totally replaced by K, and its reversal potential shifted towards more negative values. These data are consistent with the hypothesis that both Na and K ions permeate the channel, with a Na/K permeability ratio of approximately 2. Ca ions do not appear to permeate the channel, but they do have a marked inhibitory effect on the response amplitude, as do Mg ions when Ca is not present. Caffeine, intracellular acidification, and phosphodiesterase inhibitors enhance and prolong the response without changing its reversal potential. Previous studies have shown that both caffeine and intracellular acidification inhibit phosphodiesterase, and it is assumed that the common effect of these manipulations on the cAMP-induced inward current is mediated, at least partially, by the inhibition of that enzyme. In the medial cells of the pleural ganglion, this slow inward current is present, but is dominated in the depolarized cell by a cAMP-induced diminution in a Ca-activated K conductance (Kehoe, 1985b). This K conductance and, consequently, the noninverting, cAMP-induced inward current that reflects its diminution, were shown to disappear in Ca-free solutions, in the presence of isobutyl-1-methylxanthine (IBMX) or caffeine, and upon acidification of the cytoplasm. When this cAMP-sensitive K conductance is blocked, the presence of the inverting cAMP-induced cationic current is unmasked. The cAMP-induced cationic current is shown to have many properties in common with cyclic nucleotide-induced currents described in photoreceptors, olfactory receptor cilia, and cardiac myocytes, all of which have been shown to be outwardly rectifying cationic currents that are inhibited by divalent cations and do not involve the activation of a cAMP-dependent kinase.
环核苷酸与许多递质对膜电导的长期影响有关。环磷酸腺苷（cAMP）对软体动物神经元的一个先前观察到的效应是诱导一种缓慢的内向电流，本文在加州海兔胸膜神经节的去极化前侧和中间细胞中对其进行了进一步评估，以便更好地理解其潜在的离子机制及其对多种药理试剂的敏感性。这种电流似乎是在前侧细胞中观察到的唯一由cAMP诱导的电流，它在约 +25 mV 时反转，即比钠离子平衡电位（ENa）低约25 - 30 mV。当细胞外一半的钠离子被甘露醇或 N - 甲基 - D - 葡糖胺取代时，这种反转电位降低了约15 - 16 mV，而细胞外氯离子、钙离子或镁离子的变化对其没有影响。在钠离子完全被钾离子取代的海水中，该反应仍然存在，并且其反转电位向更负值移动。这些数据与钠离子和钾离子都能通透该通道的假设一致，钠离子/钾离子的通透率约为2。钙离子似乎不能通透该通道，但它们对反应幅度有显著的抑制作用，当不存在钙离子时镁离子也有同样的作用。咖啡因、细胞内酸化和磷酸二酯酶抑制剂可增强并延长该反应，而不改变其反转电位。先前的研究表明，咖啡因和细胞内酸化都能抑制磷酸二酯酶，并且假定这些操作对cAMP诱导的内向电流的共同作用至少部分是由该酶的抑制介导的。在胸膜神经节的中间细胞中，这种缓慢的内向电流存在，但在去极化细胞中，它被cAMP诱导的钙激活钾电导的减小所主导（Kehoe，1985b）。这种钾电导以及因此反映其减小的非反转的、cAMP诱导的内向电流，在无钙溶液中、在异丁基 - 1 - 甲基黄嘌呤（IBMX）或咖啡因存在时以及细胞质酸化时会消失。当这种对cAMP敏感的钾电导被阻断时，反转的cAMP诱导的阳离子电流就会显现出来。已表明cAMP诱导的阳离子电流与在光感受器、嗅觉受体纤毛和心肌细胞中描述的环核苷酸诱导的电流有许多共同特性，所有这些电流都已被证明是外向整流的阳离子电流，被二价阳离子抑制，并且不涉及cAMP依赖性激酶的激活。
