Evidence for role of acid-sensing ion channels in nucleus ambiguus neurons: essential differences in anesthetized versus awake rats.

Evidence for role of acid-sensing ion channels in nucleus ambiguus neurons: essential differences in anesthetized versus awake rats.
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DOI:
10.1007/s00360-014-0829-9
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发表时间:
2014-08
期刊:
Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology
影响因子:
--
通讯作者:
Brailoiu E
Brailoiu E
中科院分区:
其他
文献类型:
--
作者:
Brailoiu GC;Deliu E;Altmann JB;Chitravanshi V;Brailoiu E

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酸敏感离子通道(ASIC)广泛表达于包括髓质在内的多个脑区,其在生理和病理生理中的作用尚不完全清楚。我们研究了6.2的酸性pH值对参与副交感神经心脏控制的延髓神经元的影响。我们的研究结果表明,逆行标记的疑核的心脏迷走神经元去极化酸性pH值。此外,pH 6.2的酸性生理盐水增加胞浆Ca 2+浓度,促进Ca 2+内流疑核神经元。体内研究表明,向疑核中微量注射酸性人工脑脊液(pH 6.2)可降低清醒大鼠的心率,而对麻醉动物无影响。预处理与阿米洛利或benzamil,两个广泛使用的ASIC阻断剂,废除了在体外和体内的影响引起的pH 6.2。我们的研究结果支持ASIC在调节心脏迷走神经张力中的关键作用,并为酸中毒诱导的心动过缓提供了潜在机制,同时确定了麻醉和清醒大鼠对酸性pH值反应的重要差异。
Acid-sensing ion channels (ASIC) are widely expressed in several brain regions including medulla; their role in physiology and pathophysiology is incompletely understood. We examined the effect of acidic pH of 6.2 on the medullary neurons involved in parasympathetic cardiac control. Our results indicate that retrogradely-labeled cardiac vagal neurons of nucleus ambiguus are depolarized by acidic pH. In addition, acidic saline of pH 6.2 increases cytosolic Ca2+ concentration by promoting Ca2+ influx in nucleus ambiguus neurons. In vivo studies indicate that microinjection of acidic artificial cerebrospinal fluid (pH 6.2) into the nucleus ambiguus decreases the heart rate in conscious rats, whereas it has no effect in anesthetized animals. Pretreatment with either amiloride or benzamil, two widely used ASIC blockers, abolishes both the in vitro and in vivo effects elicited by pH 6.2. Our findings support a critical role for ASIC in modulation of cardiac vagal tone and provide a potential mechanism for acidosis-induced bradycardia, while identifying important differences in the response to acidic pH between anesthetized and conscious rats.
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