Effects of ATP on intracellular calcium dynamics of the perineurium of peripheral nerve bundles

Adenosine-5'-triphosphate (ATP) released from damaged cells can affect functions of adjacent cells. Injuries of peripheral tissue stimulate nerves, but effect of ATP on the nerve bundles is still speculative. Peripheral nerves are surrounded by perineurium, therefore the response of perineurium may be a first event of nerve stimulation at tissue injuries. The aim of the present study is to clarify whether the perineurium responds to ATP. To this end, we analyzed the dynamics of the intracellular calcium concentration (Ca2+]i) of perineurial cells by confocal microscopy. ATP induced a Ca2+]i increase of perineurial cells. Ca2+ channel blockers and removing of extracellular Ca2+, but not thapsigargin pretreatment, abolished ATP-induced Ca2+]i dynamics. This indicated that the Ca2+]i increase was due to an influx of extracellular Ca2+. Adenosine-5'-diphosphate also elicited an increase of Ca2+]i, but P1 receptor agonists had few effects on Ca2+]i dynamics. Suramin (an antagonist of P2X and P2Y receptors) totally inhibited ATP-induced Ca2+]i dynamics, but reactive blue 2 (a P2Y receptor antagonist) did not. Uridine-5'-triphosphate (a P2Y receptor agonist) induced no significant change in Ca2+]i, but alpha,beta-methylene ATP (a P2X receptor agonist) caused a Ca2+]i increase. In conclusion, perineurial cells respond to extracellular ATP mainly via P2X receptors.