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In mouse models of SMA, the development and maintenance of spinal motor neurons and the neuromuscular junction (NMJ) function are altered. Since nifedipine is known to be neuroprotective and increases neurotransmission in nerve terminals, we investigated its effects on cultured spinal cord motor neurons and motor nerve terminals of control and SMA mice. We found that application of nifedipine increased the frequency of spontaneous Ca2+ transients, growth cone size, cluster-like formations of Cav2.2 channels, and it normalized axon extension in SMA neurons in culture. At the NMJ, nifedipine significantly increased evoked and spontaneous release at low-frequency stimulation in both genotypes. High-strength stimulation revealed that nifedipine increased the size of the readily releasable pool (RRP) of vesicles in control but not SMA mice. These findings provide experimental evidence about the ability of nifedipine to prevent the appearance of developmental defects in SMA embryonic motor neurons in culture and reveal to which extent nifedipine could still increase neurotransmission at the NMJ in SMA mice under different functional demands.<\/jats:p>","DOI":"10.3390\/ijms24087648","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T06:06:18Z","timestamp":1682057178000},"page":"7648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nifedipine Ameliorates Cellular Differentiation Defects of Smn-Deficient Motor Neurons and Enhances Neuromuscular Transmission in SMA Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Rocio","family":"Tejero","sequence":"first","affiliation":[{"name":"Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2524-8120","authenticated-orcid":false,"given":"Mohammad","family":"Alsakkal","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neurobiology, University Hospital W\u00fcrzburg, 97078 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Hennlein","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neurobiology, University Hospital W\u00fcrzburg, 97078 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana M.","family":"Lopez-Cabello","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-3760","authenticated-orcid":false,"given":"Sibylle","family":"Jablonka","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neurobiology, University Hospital W\u00fcrzburg, 97078 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4027-4044","authenticated-orcid":false,"given":"Lucia","family":"Tabares","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and Characterization of a Spinal Muscular Atrophy-Determining Gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrn2670","article-title":"Spinal Muscular Atrophy: Why Do Low Levels of Survival Motor Neuron Protein Make Motor Neurons Sick?","volume":"10","author":"Burghes","year":"2009","journal-title":"Nat. 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