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Extracellular calcium is essential for recycling of synaptic\u2010like vesicles (SLVs) in the terminals and for the stretch\u2010evoked inward calcium current of the receptor potential. Conversely, removal of calcium from the extracellular medium abolishes stretch\u2010evoked action potentials (APs). However, the calcium channel(s) involved and mechanism(s) of action are unknown. This study begins identifying the channels involved and their actions. Specific calcium channel toxins, agonists and antagonists were examined for effects on stretch\u2010evoked muscle spindle afferent discharge, and live spindle sensory terminal labelling with FM1\u201043 was used to monitor SLV recycling in adult rat lumbrical muscle. Voltage\u2010gated calcium channels, particularly P\/Q\u2010type (Ca<jats:sub>v<\/jats:sub>2.1) and L\u2010type (Ca<jats:sub>v<\/jats:sub>1.1\u20131.4), strongly regulated the firing frequency of APs in response to a standard stretch, probably by regulating the opening of \u2018big\u2019, \u2018intermediate\u2019 and \u2018small\u2019 calcium\u2010activated potassium channels (K<jats:sub>Ca<\/jats:sub>), with direct evidence for BK (K<jats:sub>Ca<\/jats:sub>1.1), SK (most likely K<jats:sub>Ca<\/jats:sub>2.2) and IK (K<jats:sub>Ca<\/jats:sub>3.1) involvement. Moreover, calcium from two different sources regulated separate aspects of SLV recycling. Thus, L\u2010type channel blockers inhibited FM1\u201043 release, while TRPV4 (transient receptor potential, vanilloid, type 4) channel blockers entirely inhibited FM1\u201043 uptake. No role in SLV recycling was found for P\/Q type channels, and no role at all was found for N\u2010type (Ca<jats:sub>v<\/jats:sub>2.3) channels. Overall, these studies pinpoint multiple different aspects of calcium signalling, through different channel families, and produce the first evidence of a role for a mechanosensory TRPV4 channel in muscle spindle sensory terminal function.<\/jats:p>","DOI":"10.1113\/ep092558","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T13:15:14Z","timestamp":1751030114000},"page":"1457-1472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Calcium regulation of muscle spindle mechanosensory afferent function"],"prefix":"10.1113","volume":"110","author":[{"given":"Anna","family":"Simon","sequence":"first","affiliation":[{"name":"School of Medicine, Medical Sciences &amp; Nutrition University of Aberdeen  Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Lofthouse","sequence":"additional","affiliation":[{"name":"School of Medicine, Medical 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