The pool of fast releasing vesicles is augmented by myosin light chain kinase inhibition at the calyx of held synapse

Geetha Srinivasan, Hee Kim Jun, Henrique Von Gersdorff

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Synaptic strength is determined by release probability and the size of the readily releasable pool of docked vesicles. Here we describe the effects of blocking myosin light chain kinase (MLCK), a cytoskeletal regulatory protein thought to be involved in myosin-mediated vesicle transport, on synaptic transmission at the mouse calyx of Held synapse. Application of three different MLCK inhibitors increased the amplitude of the early excitatory postsynaptic currents (EPSCs) in a stimulus train, without affecting the late steady-state EPSCs. A presynaptic locus of action for MLCK inhibitors was confirmed by an increase in the frequency of miniature EPSCs that left their average amplitude unchanged. MLCK inhibition did not affect presynaptic Ca2+ currents or action potential waveform. Moreover, Ca2+ imaging experiments showed that [Ca2+]i transients elicited by 100-Hz stimulus trains were not altered by MLCK inhibition. Studies using high-frequency stimulus trains indicated that MLCK inhibitors increase vesicle pool size, but do not significantly alter release probability. Accordingly, when AMPA-receptor desensitization was minimized, EPSC paired-pulse ratios were unaltered by MLCK inhibition, suggesting that release probability remains unaltered. MLCK inhibition potentiated EPSCs even when presynaptic Ca2+ buffering was greatly enhanced by treating slices with EGTA-AM. In addition, MLCK inhibition did not affect the rate of recovery from short-term depression. Finally, developmental studies revealed that EPSC potentiation by MLCK inhibition starts at postnatal day 5 (P5) and remains strong during synaptic maturation up to P18. Overall, our data suggest that MLCK plays a crucial role in determining the size of the pool of synaptic vesicles that undergo fast release at a CNS synapse.

Original languageEnglish (US)
Pages (from-to)1810-1824
Number of pages15
JournalJournal of neurophysiology
Issue number4
StatePublished - Apr 2008

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology


Dive into the research topics of 'The pool of fast releasing vesicles is augmented by myosin light chain kinase inhibition at the calyx of held synapse'. Together they form a unique fingerprint.

Cite this