Presynaptic depolarization per se increases the transmitter release without calcium influx

Abstract

It is well established that the Ca²⁺-influx through voltage-dependent Ca²⁺ channels plays a key role in promoting the depolarization-induced release of neurotransmitters from nerve terminals. In contrast, it has also been suggested that membrane potential itself has a decisive role in controlling neurotransmitter release. Here, we report that the presynaptic depolarization in the absence of extracellular Ca²⁺ increases the glycine release at rat spinal dorsal horn neurons. In the Ca²⁺-free solution, the frequency of spontaneous inhibitory postsynaptic currents (IPSCs) recorded from mechanically dissociated rat dorsal horn neurons was increased by raising extracellular K⁺ concentration and by application of 100 μM 4-aminopyridine. The high K⁺-induced increase in spontaneous IPSC frequency under Ca²⁺-free conditions was markedly inhibited by pretreatment of BAPTA-AM, but not by nifedipine and ryanodine. Thapsigargin, a blocker of Ca²⁺-pump of internal Ca²⁺-stores, increased the spontaneous IPSC frequency even in the absence of extracellular Ca²⁺ and reduced the high K⁺-induced increase in IPSC frequency. The present results suggest that presynaptic depolarization increases the release of Ca²⁺ from internal stores, which in turn increases the glycine release in rat spinal dorsal horn. The regulation of Ca²⁺-release by depolarization per se provides a new mechanism by which neuronal activity regulates the cytosolic Ca²⁺ concentration in nerve terminals. [Jpn J Physiol 55 Suppl:S143 (2005)]