High potassium-induced facilitation of glycine release from presynaptic terminals on mechanically dissociated rat spinal dorsal horn neurons in the absence of extracellular calcium.

The high potassium-induced potentiation of spontaneous glycine release in extracellular Ca2+-free conditions was studied in mechanically dissociated rat spinal dorsal horn neurons using whole-cell patch-clamp technique. Elevating extracellular K+ concentration reversibly increased the frequency of spontaneous glycinergic inhibitory postsynaptic currents (IPSCs) in the absence of extracellular Ca2+. Blocking voltage-dependent Na+ channels (tetrodotoxin) and Ca2+ channels (nifedipine and omega-grammotoxin-SIA) had no effect on this potassium-induced potentiation of glycine-release. The high potassium-induced increase in IPSC frequency was also observed in the absence of extracellular Na+, although the recovery back to baseline levels of release was prolonged under these conditions. The action of high potassium solution on glycine release was prevented by BAPTA-AM, by depletion of intracellular Ca2+ stores by thapsigargin and by the phospholipase C inhibitor U-73122. The results suggest that the elevated extracellular K+ concentration causes Ca2+ release from internal stores which is independent of extracellular Na+- and Ca2+-influx, and may reveal a novel mechanism by which the potassium-induced depolarization of presynaptic nerve terminals can regulate intracellular Ca2+ concentration and exocytosis.