Division of Cardiovascular and Neuronal Remodelling, Leeds Institute for Genetics, Health and Therapeutics (LIGHT), Faculty of Medicine and Health, Worsley Building (Level 10), University of Leeds, Clarendon Way, Leeds LS2 9JT, UK.
Respir Physiol Neurobiol. 2010 Dec 31;174(3):292-8. doi: 10.1016/j.resp.2010.08.010. Epub 2010 Aug 22.
Hypoxic chemotransduction in the carotid body requires release of excitatory transmitters from type I cells that activate afferent sensory neurones. Transmitter release is dependent on voltage-gated Ca2+ entry which is evoked by membrane depolarization. This excitatory response to hypoxia is initiated by inhibition of specific O2 sensitive K+ channels, of which several types have been reported. Here, we discuss mechanisms which have been put forward to account for hypoxic inhibition of type I cell K+ channels. Whilst evidence indicates that one O2 sensitive K+ channel, BKCa, may be regulated by gasotransmitters (CO and H2S) in an O2-dependent manner, other studies now indicate that activation of AMP-activated protein kinase (AMPK) accounts for inhibition of both BKCa and 'leak' O2 sensitive K+ channels, and perhaps also other O2 sensitive K+ channels reported in different species. We propose that type I cell AMPK activation occurs as a result of inhibition of mitochondrial oxidative phosphorylation, and does not require increased production of reactive oxygen species. Thus, AMPK activation provides the basis for unifying the 'membrane' and 'mitochondrial' hypotheses, previously regarded as disparate, to account for hypoxic chemotransduction.
颈动脉体中的缺氧化学转导需要 I 型细胞释放兴奋性递质，这些递质激活传入感觉神经元。递质释放依赖于电压门控 Ca2+内流，这是由膜去极化引起的。这种对缺氧的兴奋性反应是由特定的 O2 敏感 K+通道的抑制引发的，已经报道了几种类型的这种通道。在这里，我们讨论了用于解释 I 型细胞 K+通道缺氧抑制的机制。虽然有证据表明一种 O2 敏感的 K+通道 BKCa 可能通过气体递质（CO 和 H2S）以 O2 依赖的方式进行调节，但其他研究现在表明，AMP 激活蛋白激酶 (AMPK) 的激活解释了 BKCa 和“泄漏”O2 敏感 K+通道的抑制，以及可能在不同物种中报道的其他 O2 敏感 K+通道的抑制。我们提出，I 型细胞 AMPK 的激活是由于线粒体氧化磷酸化的抑制，而不需要增加活性氧的产生。因此，AMPK 的激活为统一以前被认为是不同的“膜”和“线粒体”假说提供了基础，以解释缺氧化学转导。
