Donnelly D F
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06524, USA.
Respir Physiol. 1997 Nov;110(2-3):211-8. doi: 10.1016/s0034-5687(97)00085-6.
The mechanism by which the carotid body senses hypoxia and causes an increase in spiking activity on the sinus nerve is not well resolved. Most experimental attention is focused on the glomus cell, a secretory cell which is apposed to the afferent nerve endings and which is the presumed site of oxygen sensing. It is proposed that hypoxia causes glomus cell depolarization by inhibiting an oxygen-sensitive K+ current. This leads to depolarization, activation of voltage-gated calcium influx and enhanced secretion of an excitatory transmitter. At present, 4 candidate oxygen-sensitive K+ currents have been identified based on patch-clamp studies of isolated glomus cells. Recent experiments using intact carotid bodies have been undertaken to identify which current is most likely to mediate the hypoxia response. Three of the four currents are sensitive to K+ channel blocking agents (TEA, 4-AP and charybdotoxin), yet all these agents failed to mimic hypoxia, neither stimulating chemoreceptor nerve activity nor enhancing catecholamine secretion. Thus, the fourth current, a leak current which is insensitive to these agents is the most likely candidate for mediating glomus cell depolarization, but the drug-sensitivity of this current is not yet known which precludes a direct test of this speculation.
颈动脉体感知缺氧并导致窦神经放电活动增加的机制尚未完全明确。大多数实验关注的是球细胞,它是一种分泌细胞,与传入神经末梢相邻,被认为是氧感应的部位。有人提出,缺氧通过抑制氧敏感的钾电流导致球细胞去极化。这会导致去极化、电压门控钙内流的激活以及兴奋性递质分泌的增强。目前,基于对分离的球细胞的膜片钳研究,已鉴定出4种候选的氧敏感钾电流。最近使用完整颈动脉体进行的实验旨在确定哪种电流最有可能介导缺氧反应。这四种电流中的三种对钾通道阻断剂(四乙铵、4-氨基吡啶和蝎毒素)敏感,但所有这些药物都未能模拟缺氧,既未刺激化学感受器神经活动,也未增强儿茶酚胺分泌。因此,对这些药物不敏感的第四种电流,即漏电流,最有可能是介导球细胞去极化的候选电流,但该电流的药物敏感性尚不清楚,这使得无法直接验证这一推测。