ACID PH AUGMENTS EXCITATORY ACTION OF ATP ON A DISSOCIATED MAMMALIAN SENSORY NEURON

ATP stimulates nociceptive neurons via an action on ligand-gated ion c hannels. Since tissue injury and inflammation result in both localized acidosis and release of ATP, we studied the effect of acid pH on ATP- gated ion channels in rat nodose ganglion neurons. Lowering pH dramati cally increased membrane depolarization and action potential firing el icited by ATP. ATP-activated current was enhanced by acid pH and suppr essed by alkaline pH. A pH of 7.2 produced the half-maximal effect. Ac idification increased the apparent affinity of the receptor for ATP, a s evidenced by a parallel shift of the ATP concentration-response curv e to the left. The observations suggest that the localized acidosis as sociated with tissue injury may enhance pain perception via an action on ATP-gated ion channels on mammalian sensory neurons.