{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T20:14:59Z","timestamp":1784837699747,"version":"3.55.0"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,8]]},"abstract":"Abstract<\/jats:title>\n \n Background:<\/jats:title>\n The decline in voluntary muscle contraction during low-frequency nerve stimulation is used clinically to assess the type and degree of neuromuscular block. The mechanism underlying this depression is unknown.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Simultaneous electrophysiological measurements of neurotransmitter release and prejunctional Ca\n 2+<\/jats:sup>\n currents were made at mouse neuromuscular junctions to evaluate the hypothesis that decreases in nerve terminal Ca\n 2+<\/jats:sup>\n currents are responsible for low-frequency depression.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Under conditions generally used to measure Ca\n 2+<\/jats:sup>\n currents at the neuromuscular junction, increasing the frequency of nerve stimulation briefly from 0.017 to 0.1\u20131 Hz caused a simultaneous reduction in the release of the neurotransmitter acetylcholine to 52.2 \u00b1 4.4% of control and the Ca\n 2+<\/jats:sup>\n current peak to 75.4 \u00b1 2.0% of control (\n P<\/jats:italic>\n < 0.001, n = 5 experiments for both measurements, mean \u00b1 SEM for all data). In conditions used for train-of-four monitoring (4 stimuli, 2 Hz), neurotransmitter release declined to 42.0 \u00b1 1.0% of control and the Ca\n 2+<\/jats:sup>\n current peak declined to 75.8 \u00b1 3.3% of control between the first and fourth stimulus (\n P<\/jats:italic>\n < 0.001, n = 7 experiments for both measurements). Depression in acetylcholine release during train-of-four protocols also occurred in the absence of neuromuscular-blocking drugs.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion:<\/jats:title>\n \n The results demonstrate that neuromuscular depression during train-of-four monitoring is due to a decline in nerve terminal Ca\n 2+<\/jats:sup>\n currents, hence reducing the release of acetylcholine. As similar processes may come into play at higher stimulation frequencies, agents that antagonize the decline in Ca\n 2+<\/jats:sup>\n currents could be used to treat conditions in which neuromuscular depression can be debilitating.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/aln.0b013e31829083d8","type":"journal-article","created":{"date-parts":[[2013,3,27]],"date-time":"2013-03-27T10:19:33Z","timestamp":1364379573000},"page":"326-334","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Low-frequency Neuromuscular Depression Is a Consequence of a Reduction in Nerve Terminal Ca2+ Currents at Mammalian Motor Nerve Endings"],"prefix":"10.1097","volume":"119","author":[{"given":"Eugene M.","family":"Silinsky","sequence":"first","affiliation":[{"name":"Professor and Chairman, Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, 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