ATP ACTING ON P-2Y RECEPTORS TRIGGERS CALCIUM MOBILIZATION IN SCHWANN-CELLS AT THE NEUROELECTROCYTE JUNCTION IN SKATE

Schwann cells are integral cellular components of the dense cholinergi c presynaptic plexus (nerve plate) which innervates each electrocyte i n skate electric organ. Using the Ca2+-sensitive dye fura-2, we have f ollowed the response in these cells to various chemical challenges. In K+ depolarized nerve plates nerve terminals consistently responded wi th a rapid and sustained Ca2+ signal. Schwann cell responses to depola rization were rarely seen but, when observed, were always delayed in o nset when compared to nerve terminal response (6-10 a later). The poss ibility that these responses were triggered by mediators released from nerve terminals was tested by direct application of candidate substan ces. Schwann cells were found to respond to adenosine triphosphate and adenosine diphosphate with a biphasic increase of intracellular Ca2concentration, a rapid peak response being followed in the majority of cells by a sustained plateau phase. In the absence of external Ca2+ o nly the transient peak response was observed. Depletion of internal Ca 2+ stores with thapsigargin completely inhibited the adenosine triphos phate-stimulated rise in Schwann cell Ca2+. The response to adenosine triphosphate was concentration-dependent (EC50 2.8 mu M) and was rever sibly blocked by two antagonists of P-2, purinoceptors: suramin and re active blue 2. Adenosine diphosphate and 2-methylthio-adenosine tripho sphate were equipotent with adenosine triphosphate and at high concent rations (100 mu M) diadenosine tetraphosphate produced responses compa rable to low concentrations of adenosine triphosphate. Adenosine, aden osine monophosphate, the up-methylene analogues of adenosine triphosph ate and adenosine diphosphate, uridine triphosphate, cytidine triphosp hate and guanosine triphosphate were without significant effect. These results show that. in skate electric organ Schwann cells, the release of Ca2+ from intracellular stores is triggered by adenosine triphosph ate acting on P-2Y receptors and suggest that Schwann cells may be tar gets for synaptically-released adenosine triphosphate in the electric organ model of the neuromuscular junction. (C) 1997 IBRO. Published by Elsevier Science Ltd.