Swelling-activated Ca2+ channels trigger Ca2+ signals in Merkel cells.
Swelling-activated Ca2+ channels trigger Ca2+ signals in Merkel cells.
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DOI：
10.1371/journal.pone.0001750
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发表时间：
2008-03-12
期刊：
影响因子：
3.7
通讯作者：
Lumpkin EA
中科院分区：
文献类型：
--
作者：
Haeberle H;Bryan LA;Vadakkan TJ;Dickinson ME;Lumpkin EA
默克尔细胞-神经突复合体是高度敏感的触觉受体，包括表皮默克尔细胞和感觉传入。基于形态学和分子研究，默克尔细胞被认为是机械感觉细胞，通过神经传递传入信号;然而，在完整皮肤中测试这一假设的功能研究产生了相互矛盾的结果。为了在简化的系统中测试该模型，我们询问纯化的默克尔细胞是否通过机械刺激直接活化。细胞形状与不等渗溶液的变化和反应进行了监测与Fura-2的Ca 2+成像。我们发现，低渗诱导的细胞肿胀，但不是高渗溶液，触发细胞质Ca 2+瞬变。一些证据表明，这些信号来自肿胀激活的Ca 2+渗透性离子通道。首先，通过螯合细胞外Ca 2+可逆地消除瞬变，证明需要Ca 2+穿过质膜流入。第二，Ca 2+瞬变最初观察到质膜附近的细胞质过程。第三，电压激活的Ca 2+通道（VACC）拮抗剂减少了一半的瞬变，这表明肿胀激活的通道解除质膜激活VACC。最后，清空内部Ca 2+存储衰减瞬变80%，这表明Ca 2+从存储释放增强膨胀激活的Ca 2+信号。为了确定候选的机械转导通道，我们使用RT-PCR扩增离子通道转录本，其药理学特征与默克尔细胞中低渗诱发的Ca 2+信号相匹配。我们发现了11个扩增子，包括PKD 1，PKD 2和TRPC 1，以前在其他细胞中涉及机械转导的通道。总的来说，这些结果直接证明了默克尔细胞被低渗诱发的肿胀激活，鉴定了介导这些反应的细胞信号传导机制，并支持了默克尔细胞有助于默克尔细胞-神经突复合体中的触摸接收的假设。
Merkel cell-neurite complexes are highly sensitive touch receptors comprising epidermal Merkel cells and sensory afferents. Based on morphological and molecular studies, Merkel cells are proposed to be mechanosensory cells that signal afferents via neurotransmission; however, functional studies testing this hypothesis in intact skin have produced conflicting results. To test this model in a simplified system, we asked whether purified Merkel cells are directly activated by mechanical stimulation. Cell shape was manipulated with anisotonic solution changes and responses were monitored by Ca2+ imaging with fura-2. We found that hypotonic-induced cell swelling, but not hypertonic solutions, triggered cytoplasmic Ca2+ transients. Several lines of evidence indicate that these signals arise from swelling-activated Ca2+-permeable ion channels. First, transients were reversibly abolished by chelating extracellular Ca2+, demonstrating a requirement for Ca2+ influx across the plasma membrane. Second, Ca2+ transients were initially observed near the plasma membrane in cytoplasmic processes. Third, voltage-activated Ca2+ channel (VACC) antagonists reduced transients by half, suggesting that swelling-activated channels depolarize plasma membranes to activate VACCs. Finally, emptying internal Ca2+ stores attenuated transients by 80%, suggesting Ca2+ release from stores augments swelling-activated Ca2+ signals. To identify candidate mechanotransduction channels, we used RT-PCR to amplify ion-channel transcripts whose pharmacological profiles matched those of hypotonic-evoked Ca2+ signals in Merkel cells. We found 11 amplicons, including PKD1, PKD2, and TRPC1, channels previously implicated in mechanotransduction in other cells. Collectively, these results directly demonstrate that Merkel cells are activated by hypotonic-evoked swelling, identify cellular signaling mechanisms that mediate these responses, and support the hypothesis that Merkel cells contribute to touch reception in the Merkel cell-neurite complex.
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