A HCO(3)(-)-dependent mechanism involving soluble adenylyl cyclase for the activation of Ca²⁺ currents in locus coeruleus neurons.
A HCO(3)(-)-dependent mechanism involving soluble adenylyl cyclase for the activation of Ca²⁺ currents in locus coeruleus neurons.
复制标题
一种 HCO(3)(-) 依赖性机制，涉及可溶性腺苷酸环化酶，用于激活蓝斑神经元中的 Ca2+ 电流。
DOI：
10.1016/j.bbadis.2014.07.027
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Putnam,RobertW
中科院分区：
文献类型：
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作者：
Imber,AnnN;Santin,JosephM;Graham,CathyD;Putnam,RobertW
高碳酸血症会激活 Ca2+ 通道并增加蓝斑神经元的细胞内 Ca2+ 水平，蓝斑是已知的参与呼吸控制的化学敏感区域。我们还表明，大电导 Ca2+ 激活的 K+ 通道与该通路结合，限制了高碳酸血症引起的蓝斑神经元放电率的增加。在这里，我们提供的证据表明 Ca2+ 电流是由 HCO3− 敏感途径激活的。与高碳酸血症相关的 HCO3 增加会激活 HCO3 敏感的腺苷酸环化酶（可溶性腺苷酸环化酶）。这导致环单磷酸腺苷水平增加，并通过环单磷酸腺苷激活蛋白激酶 A 激活 Ca2+ 通道。我们还表明，蓝斑神经元细胞质中存在可溶性腺苷酸环化酶，并且环单磷酸腺苷类似物 db-环单磷酸腺苷增加 钙离子。通过在酸化过程中降低 HCO3−水平或抑制可溶性腺苷酸环化酶或蛋白激酶 A（但不抑制跨膜腺苷酸环化酶）来破坏该通路，可以增加老年新生儿蓝斑神经元对高碳酸血症的放电率反应幅度，其程度与抑制 K+ 通道相同。本文是题为“可溶性腺苷酸环化酶在健康和疾病中的作用”的特刊的一部分。
Hypercapnic acidosis activates Ca2+channels and increases intracellular Ca2+levels in neurons of the locus coeruleus, a known chemosensitive region involved in respiratory control. We have also shown that large conductance Ca2+-activated K+channels, in conjunction with this pathway, limits the hypercapnic-induced increase in firing rate in locus coeruleus neurons. Here, we present evidence that the Ca2+current is activated by a HCO3−-sensitive pathway. The increase in HCO3−associated with hypercapnia activates HCO3−-sensitive adenylyl cyclase (soluble adenylyl cyclase). This results in an increase in cyclic adenosine monophosphate levels and activation of Ca2+channels via cyclic adenosine monophosphate-activated protein kinase A. We also show the presence of soluble adenylyl cyclase in the cytoplasm of locus coeruleus neurons, and that the cyclic adenosine monophosphate analogue db-cyclic adenosine monophosphate increases Ca2+i. Disrupting this pathway by decreasing HCO3−levels during acidification or inhibiting either soluble adenylyl cyclase or protein kinase A, but not transmembrane adenylyl cyclase, can increase the magnitude of the firing rate response to hypercapnia in locus coeruleus neurons from older neonates to the same extent as inhibition of K+channels. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease.