Pregnenolone sulfate enhances spontaneous glutamate release via the induction of presynaptic Ca2+-induced Ca2+ release : 해마 hilar 신경세포에서 Pregnenolone sulfate에 의한 자발적 글루타민산 방출 증가

다국어 초록 (Multilingual Abstract)

Pregnenolone sulfate (PS) acts as an excitatory neuromodulator and has a variety of neuropharmacological actions, such as memory enhancing and convulsant effects. In the present study, we have investigated the effect of PS on glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) in acutely isolated dentate gyrus hilar neurons by use of a conventional whole-cell patch-clamp technique. PS significantly increased sEPSC frequency in a dose-dependent manner without affecting the current amplitude, suggesting that PS acts presynaptically to increase the probability of spontaneous glutamate release. However, known molecular targets of PS, such as ??7 nicotinic ACh, NMDA, ??1 receptors and voltage-dependent Ca2+ channels, were not responsible for the PS-induced increase in sEPSC frequency. Whereas, the PS-induced increase in sEPSC frequency was completely occluded in the Ca2+-free external solution, and significantly reduced by either the depletion of presynaptic Ca2+ stores or the blockade of ryanodine receptors, suggesting that PS elicits Ca2+-induced Ca2+ release (CICR) within glutamatergic nerve terminals. In addition, the PS-induced increase in sEPSC frequency was completely occluded by transient receptor potential (TRP) channel blockers. These data suggest that PS increases spontaneous glutamate release onto acutely isolated hilar neurons via presynaptic CICR, which was triggered by the Ca2+ influx passing through presynaptic TRP channels. The PS-induced modulation of excitatory transmission onto hilar neurons would have a broad impact on the excitability of hilar neurons and thus affect the pathophysiological functions mediated by the hippocampus.

목차 (Table of Contents)

• 1. Introduction 1
• 2. Materials and Methods 4
• 3. Results 8
• 4. Discussion 25
• 5. Summary 32
• 6. References 33