ATP acting on P 2Y receptors triggers calcium mobilization in Schwann cells at the neuroelectrocyte junction in skate

Abstract

Schwann cells are integral cellular components of the dense cholinergic presynaptic plexus (nerve plate) which innervates each electrocyte in skate electric organ. Using the Ca 2+-sensitive dye fura-2, we have followed the response in these cells to various chemical challenges. In K + depolarized nerve plates nerve terminals consistently responded with a rapid and sustained Ca 2+ signal. Schwann cell responses to depolarization were rarely seen but, when observed, were always delayed in onset when compared to nerve terminal response (6–10 s later). The possibility that these responses were triggered by mediators released from nerve terminals was tested by direct application of candidate substances. Schwann cells were found to respond to adenosine triphosphate and adenosine diphosphate with a biphasic increase of intracellular Ca 2+ concentration, a rapid peak response being followed in the majority of cells by a sustained plateau phase. In the absence of external Ca 2+ only the transient peak response was observed. Depletion of internal Ca 2+ stores with thapsigargin completely inhibited the adenosine triphosphate-stimulated rise in Schwann cell Ca 2+. The response to adenosine triphosphate was concentration-dependent (EC 50 2.8 μM) and was reversibly blocked by two antagonists of P 2 purinoceptors: suramin and reactive blue 2. Adenosine diphosphate and 2-methylthio-adenosine triphosphate were equipotent with adenosine triphosphate and at high concentrations (100 μM) diadenosine tetraphosphate produced responses comparable to low concentrations of adenosine triphosphate. Adenosine, adenosine monophosphate, the α β-methylene analogues of adenosine triphosphate and adenosine diphosphate, uridine triphosphate, cytidine triphosphate and guanosine triphosphate were without significant effect. These results show that, in skate electric organ Schwann cells, the release of Ca 2+ from intracellular stores is triggered by adenosine triphosphate acting on P 2Y receptors and suggest that Schwann cells may be targets for synaptically-released adenosine triphosphate in the electric organ model of the neuromuscular junction.