Characterization of acid‐signaling in rat vagal pulmonary sensory neurons

Abstract

Local tissue acidosis frequently occurs in airway inflammatory and ischemic conditions. The effect of physiological/pathophysiological-relevant low pH (7.0 to 5.5) on isolated rat vagal pulmonary sensory neurons was investigated using whole-cell perforated patch-clamp recordings. In voltage-clamp recordings, pulmonary sensory neurons exhibited distinct pH sensitivity and different phenotypes of inward current in responding to acidic challenge. The current evoked by pH 7.0 consisted of only a transient, rapidly inactivating component with small amplitude. The amplitude of this transient current increased when the proton concentration increased. In addition, a slow, sustained inward current began to emerge when pH ≤ 6.5 was applied. The I–V curve indicated that the transient component of acid-elicited current was carried predominantly by Na+ which was dose-dependently inhibited by amiloride, a common blocker of acid-sensing ion channels (ASICs); whereas the sustained component was significantly attenuated by capsazepine, a selective antagonist of transient receptor potential vanilloid 1 (TRPV1). Furthermore, these two components of acid-elicited current also displayed distinct recovery kinetics from desensitization. In current-clamp recordings, transient extracellular acidification depolarized the membrane potential and generated action potentials in these neurons. In summary, our results have demonstrated that low pH can stimulate rat vagal pulmonary sensory neurons through the activation of both ASICs and TRPV1. The relative roles of these two current species depend on the range of pH and vary between neurons. (Funded by NIH grants HL58686 and HL67379, the Parker B. Francis Fellowship in Pulmonary Research and Kentucky Lung Cancer Research Program)