The effects of presynaptic calcium channel modulation by roscovitine on transmitter release at the adult frog neuromuscular junction

Soyoun Cho, Stephen D. Meriney

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Calcium (Ca2+) influx through presynaptic calcium channels triggers transmitter release, and any alterations in the gating of these calcium channels results in changes in the magnitude of transmitter released. We used (R)-roscovitine, a cyclin-dependent kinase inhibitor that also appears to act directly on calcium channels, as a tool to modulate presynaptic calcium influx and study effects on transmitter release. We show that this compound increased the quantal content of acetylcholine released from the Rana frog motor nerve terminal (by 149%) without changing paired-pulse facilitation (under low calcium conditions). In contrast, exposure to 3,4-diaminopyridine (DAP; which similarly affects transmitter release by partially blocking potassium channels, altering the shape of the presynaptic action potential, and indirectly increasing calcium entry) increased paired-pulse facilitation (by 23%). In addition, we show that (R)-roscovitine predominately slowed deactivation kinetics of calcium current (by 427%) recorded from Xenopus frog motoneurons, and as a result, increased the integral of calcium channel current evoked by a physiological action potential waveform (by 44%). Because we did not observe any significant effects of structurally related cyclin-dependent kinase inhibitors [(S)-roscovitine or olomoucine] on evoked transmitter release or calcium current kinetics, it appears that these effects of (R)-roscovitine are independent of cyclin-dependent kinases (cdks). In summary, we hypothesize that (R)-roscovitine effects on transmitter release at the adult frog neuromuscular junction (NMJ) are mediated by its effects on calcium channel gating, and these effects increase our understanding of calcium triggered secretion at this synapse.

Original languageEnglish (US)
Pages (from-to)3200-3208
Number of pages9
JournalEuropean Journal of Neuroscience
Volume23
Issue number12
DOIs
Publication statusPublished - Jun 1 2006

    Fingerprint

Keywords

  • Calcium
  • Motoneuron
  • Paired-pulse facilitation Rana pipiens
  • Xenopus laevis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this