Abstract
Degradation of GTP by GTPase is thought to be essential for synaptic vesicle recycling. For example, in the endocytic process, the non-hydrolyzable GTP analogue GTPγS blocks the dynamin-dependent fission of synaptic vesicles. At the calyx of Held synapse, GTPγS loaded into the nerve terminal blocks recovery of synaptic responses from the use-dependent depression. To address whether these phenomena are co-related, we made capacitance measurements from the calyx of Held presynaptic terminal visually identified in brainstem slices of juvenile rats. A depolarizing command pulse (from –80 mV to 0 mV, 10ms) induced a rapid increase in capacitance followed by a slow recovery, suggesting that they represent vesicular exo- and endocytosis, respectively. When the presynaptic pipette contained GTP (0.3 mM) or GDPβS (3 mM), the shape and peak amplitude of the capacitance change remained stable at least for 24 min (12 stimuli). However, in the presence of GTPγS (0.2 mM) in the patch pipette, the capacitance change no longer recovered, and its peak underwent a use-dependent decline. The proline-rich domain peptide of dynamin included in the presynaptic pipette (together with GTP) mimicked the effects of GTPγS. We conclude that the dynamin-dependent GTP hydrolysis plays an essential role in vesicle endocytosis, thereby contributing to the recovery from use-dependent synaptic depression. [Jpn J Physiol 54 Suppl:S148 (2004)]
