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首页> 外文期刊>American Journal of Physiology >KCa1.1 channel contributes to cell excitability in unmyelinated but not myelinated rat vagal afferents.
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KCa1.1 channel contributes to cell excitability in unmyelinated but not myelinated rat vagal afferents.

机译：KCA1.1通道有助于在未封闭但不含肢体大鼠缩小传神中的细胞兴奋性。

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摘要

High conductance calcium-activated potassium (BK(Ca)) channels can modulate cell excitability and neurotransmitter release at synaptic and afferent terminals. BK(Ca) channels are present in primary afferents of most, if not, all internal organs and are an intriguing target for pharmacological manipulation of visceral sensation. Our laboratory has a long-standing interest in the neurophysiological differences between myelinated and unmyelinated visceral afferent function. Here, we seek to determine whether there is a differential distribution of BK(Ca) channels in myelinated and unmyelinated vagal afferents. Immunocytochemistry studies with double staining for the BK-type K(Ca)1.1 channel protein and isolectin B4 (IB4), a reliable marker of unmyelinated peripheral afferents, reveal a pattern of IB4 labeling that strongly correlates with the expression of the K(Ca)1.1 channel protein. Measures of cell size and immunostaining intensity for K(Ca)1.1 and IB4 cluster into two statistically distinct (P < 0.05) populations of cells. Smaller diameter neurons most often presented with strong IB4 labeling and are presumed to be unmyelinated (n = 1,390) vagal afferents. Larger diameter neurons most often lacked or exhibited a very weak IB4 labeling and are presumed to be myelinated (n = 58) vagal afferents. Complimentary electrophysiological studies reveal that the BK(Ca) channel blockers charybdotoxin (ChTX) and iberiotoxin (IbTX) bring about a comparable elevation in excitability and action potential widening in unmyelinated neurons but had no effect on the excitability of myelinated vagal afferents. This study is the first to demonstrate using combined immunohistochemical and electrophysiological techniques that K(Ca)1.1 channels are uniquely expressed in unmyelinated C-type vagal afferents and do not contribute to the dynamic discharge characteristics of myelinated A-type vagal afferents. This unique functional distribution of BK-type K(Ca) channels may provide an opportunity for afferent selective pharmacological intervention across a wide range of visceral pathophysiologies, particularly those with a reflexogenic etiology and pain.
机译：高电导钙活化钾（BK（CA））通道可以调节突触和传入终端的细胞兴奋性和神经递质释放。 BK（CA）通道存在于大多数内部的主要传统中，如果不是，所有内脏器官，并且是内脏感应的药理操纵的有趣目标。我们的实验室对眼部和未锁定的内脏传入功能之间的神经生理学差异具有长期兴趣。在这里，我们寻求确定肢体髓鞘和未锁定的缩小传入中的BK（CA）频道是否存在差异分布。具有双染色的BK型K（CA）的免疫细胞化学研究1.1通道蛋白和分离释蛋白B4（IB4），一种无髓外周期发育的可靠标记，揭示了与K（CA）的表达强烈相关的IB4标记的图案1.1通道蛋白。用于K（CA）1.1和IB4簇的细胞大小和免疫染色强度的测量分为两个统计学上不同的（P <0.05）细胞群。较小的直径神经元通常呈现出强IB4标记，并被推测为未浸润的（n = 1,390）缩小引入。最大直径的神经元最常见或表现出非常弱的IB4标记，并被推测为髓鞘（n = 58）缩小引入。互补的电生理学研究表明，BK（CA）通道阻滞剂Charybdotoxin（CHTX）和Iberiotoxin（IBTX）在未封闭神经元的兴奋性和动作潜力中引入了可比的升高，但对骨髓凹陷的神经构的兴奋性没有影响。本研究是第一个使用COMONELINED C型缩小引交唯一表达K（CA）1.1通道的使用组合免疫组织化学和电生理学技术的表明。这种独特的BK-型K（CA）通道的功能分布可以提供跨各种内脏病理学干预的传入选择性药理学干预，特别是那些具有反源性病因和疼痛的机会。

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