Blockade of acid sensing ion channels attenuates the exercise pressor reflex in cats
Blockade of acid sensing ion channels attenuates the exercise pressor reflex in cats
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DOI：
10.1113/jphysiol.2007.129197
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发表时间：
2007-06-15
影响因子：
5.5
通讯作者：
Kaufman, Marc P.
中科院分区：
文献类型：
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作者：
Hayes, Shawn G.;Kindig, Angela E.;Kaufman, Marc P.
虽然细纤维肌肉传入具有酸敏感离子通道（ASIC），其对运动升压反射的贡献尚不清楚。这种信息的缺乏部分归因于没有已知的ASIC的体内选择性拮抗剂的事实。虽然阿米洛利已被证明可以拮抗ASIC，但它也被证明可以拮抗电压门控钠通道，从而损害感觉神经中的冲动传导。我们的目的是测试的假设，乳酸在运动肌肉中的积累作用于ASIC位于细纤维肌肉传入唤起运动升压反射的代谢成分。为了验证这一假设，我们确定在去大脑猫，如果阿米洛利衰减静态收缩，肌腱拉伸和动脉注射乳酸和辣椒素的升压和心脏加速反应。我们发现阿米洛利剂量（0.5 μ g kg（-1）; I.A.）这减弱了对收缩和乳酸注射的升压和心脏加速反应，但对牵拉和辣椒素的反应没有影响。高剂量阿米洛利（5 μ g·kg ~（-1），I.A.）不仅阻断了对乳酸和收缩的升压和心脏加速反应，而且还减弱了对拉伸和辣椒素的反应，ASIC可能在这些动作中没有发挥重要作用。此外，我们发现低剂量的阿米洛利（0.5 μ g kg（-1））对肌梭对肌腱拉伸和琥珀胆碱的反应没有影响，而高剂量（5 μ g kg（-1））则减弱了对两者的反应。我们的数据表明，在我们的实验中使用的低剂量阿米洛利选择性地阻断ASIC，而高剂量阻断ASIC和肌肉传入冲动传导。我们的结论是，ASIC在运动加压反射的代谢成分中发挥作用。
Although thin fibre muscle afferents possess acid sensing ion channels (ASICs), their contribution to the exercise pressor reflex is not known. This lack of information is partly attributable to the fact that there is no known selective in vivo antagonist for ASICs. Although amiloride has been shown to antagonize ASICs, it also has been shown to antagonize voltage-gated sodium channels, thereby impairing impulse conduction in sensory nerves. Our aim was to test the hypothesis that lactic acid accumulation in exercising muscle acted on ASICs located on thin fibre muscle afferents to evoke the metabolic component of the exercise pressor reflex. To test this hypothesis, we determined in decerebrate cats if amiloride attenuated the pressor and cardioaccelerator responses to static contraction, to tendon stretch and to arterial injections of lactic acid and capsaicin. We found a dose of amiloride (0.5 mu g kg(-1); I.A.) that attenuated the pressor and cardioaccelerator responses to both contraction and lactic acid injection, but had no effect on the responses to stretch and capsaicin. A higher dose of amiloride (5 mu g kg(-1), I.A.) not only blocked the pressor and cardioaccelerator responses to lactic acid and contraction, but also attenuated the responses to stretch and to capsaicin, manoeuvers in which ASICs probably play no significant role. In addition, we found that the low dose of amiloride (0.5 mu g kg(-1)) had no effect on the responses of muscle spindles to tendon stretch and to succinylcholine, whereas the high dose (5 mu g kg(-1)) attenuated the responses to both. Our data suggest the low dose of amiloride used in our experiments selectively blocked ASICs, whereas the high dose blocked ASICs and impulse conduction in muscle afferents. We conclude that ASICs play a role in the metabolic component of the exercise pressor reflex.