Wyatt C N, Wright C, Bee D, Peers C
Department of Pharmacology, Leeds University, United Kingdom.
Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):295-9. doi: 10.1073/pnas.92.1.295.
Carotid body-mediated ventilatory increases in response to acute hypoxia are attenuated in animals reared in an hypoxic environment. Normally, O2-sensitive K+ channels in neurosecretory type I carotid body cells are intimately involved in excitation of the intact organ by hypoxia. We have therefore studied K+ channels and their sensitivity to acute hypoxia (PO2 12-20 mmHg) in type I cells isolated from neonatal rats born and reared in normoxic and hypoxic environments. When compared with cells from normoxic rats, K+ current density in cells from hypoxic rats was significantly reduced, whereas Ca2+ current density was unaffected. Charybdotoxin (20 nM) inhibited K+ currents in cells from normoxic rats by approximately 25% but was without significant effect in cells from hypoxic rats. However, hypoxia caused similar, reversible inhibitions of K+ currents in cells from the two groups. Resting membrane potentials (measured at 37 degrees C using the perforated-patch technique) were similar in normoxic and hypoxic rats. However, although acute hypoxia depolarized type I cells of normoxic rats, it was without effect on membrane potential in type I cells from hypoxic animals. Charybdotoxin (20 nM) also depolarized cells from normoxic rats. Our results suggest that type I cells from chronically hypoxic rats, like normoxic rats, possess O2-sensing mechanisms. However, they lack charybdotoxin-sensitive K+ channels that contribute to resting membrane potential in normoxically reared rats, and this appears to prevent them from depolarizing (and hence triggering Ca2+ influx and neurosecretion) during acute hypoxia.
在低氧环境中饲养的动物，其颈动脉体介导的对急性低氧的通气增加反应减弱。正常情况下，神经分泌型I型颈动脉体细胞中的氧敏感钾通道与低氧对完整器官的兴奋密切相关。因此，我们研究了从出生并饲养在常氧和低氧环境中的新生大鼠分离出的I型细胞中的钾通道及其对急性低氧（PO2 12 - 20 mmHg）的敏感性。与常氧大鼠的细胞相比，低氧大鼠细胞中的钾电流密度显著降低，而钙电流密度未受影响。大蝎毒素（20 nM）抑制常氧大鼠细胞中的钾电流约25%，但对低氧大鼠细胞无显著影响。然而，低氧对两组细胞中的钾电流产生相似的、可逆的抑制作用。常氧和低氧大鼠的静息膜电位（使用穿孔膜片钳技术在37℃测量）相似。然而，尽管急性低氧使常氧大鼠的I型细胞去极化，但对低氧动物的I型细胞的膜电位没有影响。大蝎毒素（20 nM）也使常氧大鼠的细胞去极化。我们的结果表明，长期低氧大鼠的I型细胞与常氧大鼠一样，具有氧传感机制。然而，它们缺乏对大蝎毒素敏感的钾通道，而这种通道在常氧饲养的大鼠中有助于静息膜电位，这似乎使它们在急性低氧期间无法去极化（从而触发钙内流和神经分泌）。
