There are possibly multiple pH sensitive chemoreceptors in the central nervous system. Recent findings showed that a fall of pH activates a distinct class of cation channels, the acid-sensing ion channels (ASICs) in peripheral and central nervous system (Akaike and Ueno 1994). On the other hand, the two-pore domain weakly inward rectifying K+ channel (TWIK)-related acid-sensitive potassium (TASK) is pH sensitive channel (Talley et al. 2000) too. Respiratory chemosensitivity seems to arise from interactions of multiple mechanisms, rather than a single unique channel, it has been documented that above mentioned pH sensitive channels may express in a single neuron (Chernov et al. 2010). ASIC1 in lateral hypothalamus contributes to breathing control (Song et al, 2012). But little is known about the composed influences of ASICs and TASK on respiratory regulation. This study investigated the cooperation of ASICs and TASK-1 in central respiratory regulation; they are both acid-sensing ion channels, the former for Na+, and the latter for K+. Sprague-Dawley rats (250-350g, n=8) of either sex were performed in the experiment. Rats were anaesthetized by intraperitoneal administration of 20% urethane (7ml/kg). Artificial cerebrospinal fluid (ACSF) with different pH values (pH = 5.5, 6.5, 7.4, 8.0 respectively, 0.1ul), Amiloride (1.0mM, 0.1ul, the blockade of ASICs), and Arachidonylethanolamide (AEA, 0.92g/mL, 0.1ul, the blockade of TASK-1), were respectively or jointly administered into lateral ventricle (LV) to observe the changes of respiratory activities via phrenic nerve discharge (PND) and its integration (PNDI). The respiratory excitability was increased as pH of ACSF decreased, significantly by pH 5.5 ACSF (P<0.05, ANOVAs). A convex concentration-effect curve of AEA was achieved within the concentration range from 10% to 100% at pH7.4. The AEA (50%) excited respiration significantly at pH 7.4 (P<0.05, ANOVAs), whereas Amiloride (1mM) inhibited it, though insignificantly. In contrast, the AEA didn’t significantly excite the activated respiration at pH 5.5, while Amiloride inhibited it significantly (P<0.05, ANOVAs). The joint blockings of ASICs and TASK-1 resulted in the effect in-between that of respective blocking of these channels at both pH 7.4 and pH 5.5. The combined effect of Amiloride and AEA suggest that, medications targeted on ASICs and TASK-1 have opposite effects on phrenic nerve output. These two pH sensitive channels play a concerted role in central chemosensitivity during physiological and pathophysiological changes.