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首页> 外文期刊>The European Journal of Neuroscience >Cyclic nucleotide-dependent ionic currents in olfactory receptor neurons of the hawkmoth Manduca sexta suggest pull-push sensitivity modulation
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Cyclic nucleotide-dependent ionic currents in olfactory receptor neurons of the hawkmoth Manduca sexta suggest pull-push sensitivity modulation

机译：Hawkmoth Manduca Sexta嗅觉受体神经元中循环核苷酸依赖性离子电流提示拉推敏感性调制

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摘要

Olfactory receptor neurons (ORNs) of the hawkmoth Manduca sexta sensitize via cAMP- and adapt via cGMP-dependent mechanisms. Perforated patch clamp recordings distinguished 11 currents in these ORNs. Derivatives of cAMP and/or cGMP antagonistically affected three of five K~+ currents and two non-specific cation currents. The Ca~2+-dependent K~+ current I_K(Ca~2+) and the sensitive pheromone-dependent K~+ current I_K(cgmp-) which both express fast kinetics, were inhibited by 8bcGMP, while a slow K+ current, I_K(cgmp+) was activated by 8bcGMP. Furthermore, application of 8bcAMP blocked slowly activating, zero mV-reversing, non-specific cation currents, I_LL and I_cat (pkc?), which remained activated in the presence of 8bcGMP. Their activations pull the membrane potential towards their 0-mV reversal potentials, in addition to increasing intracellular Ca~2+ levels voltage- and I_LL-dependently. Twenty minutes after application, 8bcGMP blocked a TEA-independent K~+ current, I_K(noTEA), and a fast cation current, I_cat(nRP), which both shift the membrane potential to negative values. We conclude that conditions of sensiti-zation are maintained at high levels of cAMP, via specific opening/closure of ion channels that allow for fast kinetics, hyperpolarized membrane potentials, and low intracellular Ca~2+ levels. In contrast, adaptation is supported via cGMP, which antagonizes cAMP, opening Ca~2+-permeable channels with slow kinetics that stabilize depolarized resting potentials. The antagonistic modulation of peripheral sensory neurons by cAMP or cGMP is reminiscent of pull-push mechanisms of neuromodulation at central synapses underlying metaplasticity.
机译：天蛾嗅觉受体神经元（ORN）通过cAMP敏感，并通过cGMP依赖机制适应。穿孔膜片钳记录区分了这些新生儿的11种电流。cAMP和/或cGMP的衍生物对五种K+电流中的三种和两种非特异性阳离子电流产生拮抗作用。8bcGMP抑制了表达快速动力学的Ca~（2+）依赖性K~+电流I_K（Ca~（2+）和敏感的信息素依赖性K~+电流I_K（cgmp-），而激活了缓慢的K~+电流I_K（cgmp+）。此外，8bcAMP的应用阻断了缓慢激活、零mV反转、非特异性阳离子电流、I_LL和I_cat（pkc？），在cGMP存在时仍保持激活状态。它们的激活将膜电位拉向其0-mV的反转电位，此外，细胞内Ca~2+水平也会随电压和I_LL的增加而增加。应用20分钟后，8bcGMP阻断了与茶无关的K~+电流I_K（noTEA）和快速阳离子电流I_cat（nRP），这两种电流都将膜电位转变为负值。我们的结论是，通过特定的离子通道开放/关闭，高水平的cAMP可以维持致敏条件，从而实现快速动力学、超极化膜电位和低细胞内Ca~2+水平。相反，适应性是通过cGMP支持的，cGMP拮抗cAMP，以缓慢的动力学打开Ca~2+渗透通道，稳定去极化静息电位。cAMP或cGMP对外周感觉神经元的拮抗性调节使人联想到中枢突触的神经调节的拉-推机制。

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