{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:45:26Z","timestamp":1773006326863,"version":"3.50.1"},"reference-count":64,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,4,12]],"date-time":"2014-04-12T00:00:00Z","timestamp":1397260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Calcium activity has been implicated in many neurodevelopmental events, including the specification of neurotransmitter phenotypes. Higher levels of calcium activity lead to an increased number of inhibitory neural phenotypes, whereas lower levels of calcium activity lead to excitatory neural phenotypes. Voltage\u2010gated calcium channels (VGCCs) allow for rapid calcium entry and are expressed during early neural stages, making them likely regulators of activity\u2010dependent neurotransmitter phenotype specification. To test this hypothesis, multiplex fluorescent in situ hybridization was used to characterize the coexpression of eight VGCC \u03b11 subunits with the excitatory and inhibitory neural markers <jats:italic>xVGlut1<\/jats:italic> and <jats:italic>xVIAAT<\/jats:italic> in <jats:italic>Xenopus laevis<\/jats:italic> embryos. VGCC coexpression was higher with <jats:italic>xVGlut1<\/jats:italic> than <jats:italic>xVIAAT<\/jats:italic>, especially in the hindbrain, spinal cord, and cranial nerves. Calcium activity was also analyzed on a single\u2010cell level, and spike frequency was correlated with the expression of VGCC \u03b11 subunits in cell culture. Cells expressing <jats:italic>Ca<jats:sub>v<\/jats:sub>2.1<\/jats:italic> and <jats:italic>Ca<jats:sub>v<\/jats:sub>2.2<\/jats:italic> displayed increased calcium spiking compared with cells not expressing this marker. The VGCC antagonist diltiazem and agonist (\u2212)BayK 8644 were used to manipulate calcium activity. Diltiazem exposure increased the number of glutamatergic cells and decreased the number of \u03b3\u2010aminobutyric acid (GABA)ergic cells, whereas (\u2212)BayK 8644 exposure decreased the number of glutamatergic cells without having an effect on the number of GABAergic cells. Given that the expression and functional manipulation of VGCCs are correlated with neurotransmitter phenotype in some, but not all, experiments, VGCCs likely act in combination with a variety of other signaling factors to determine neuronal phenotype specification. J. Comp. Neurol. 522:2518\u20132531, 2014. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/cne.23547","type":"journal-article","created":{"date-parts":[[2014,1,29]],"date-time":"2014-01-29T20:27:37Z","timestamp":1391027257000},"page":"2518-2531","source":"Crossref","is-referenced-by-count":10,"title":["The role of voltage\u2010gated calcium channels in neurotransmitter phenotype specification: Coexpression and functional analysis in <i>Xenopus laevis<\/i>"],"prefix":"10.1002","volume":"522","author":[{"given":"Brittany B.","family":"Lewis","sequence":"first","affiliation":[{"name":"Department of Biology College of William and Mary Williamsburg Virginia 23185"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren E.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biology College of William and Mary Williamsburg Virginia 23185"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy A.","family":"Herbst","sequence":"additional","affiliation":[{"name":"Department of Biology College of William and Mary Williamsburg Virginia 23185"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret S.","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Biology College of William and Mary Williamsburg Virginia 23185"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,4,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2009.02.004"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02518"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.12.005"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.51.5.872"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a003947"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R112.411645"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4264-08.2009"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.20.4547"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043661802002360"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063395"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07569"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-7-110"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0951-04.2005"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.4.1.10364"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-11-12"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-133X(03)00057-7"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-11-06325.1994"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2002.87.5.2562"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2519-09.2009"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101488108"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5098-10.2011"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20894"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23119"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.15245"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0305974101"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2142-12.2013"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2011.06.032"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.12.007"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00155"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22102"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20900"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2012.09.018"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.03.063"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2582"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-012-9290-y"},{"key":"e_1_2_8_37_1","article-title":"Dissection, culture, and analysis of Xenopus laevis embryonic retinal tissue","volume":"70","author":"McDonough MJ","year":"2012","journal-title":"J Vis Exp"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.11.036"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.26.12639"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.02.008"},{"key":"e_1_2_8_41_1","volume-title":"Normal table of Xenopus laevis (Daudin)","author":"Nieuwkoop P","year":"1994"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2255"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2864"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M710544200"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20889"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a004259"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2011.12.009"},{"key":"e_1_2_8_48_1","volume-title":"Molecular cloning","author":"Sambrook J","year":"2001"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0967199408005108"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1459"},{"key":"e_1_2_8_51_1","volume-title":"Early development of Xenopus laevis: a laboratory manual","author":"Sive H","year":"2000"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3154"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(02)00330-6"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2005.01.021"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.007"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-169X.2010.01220.x"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.268722"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-011-9270-9"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.5.5.16473"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2012.11.013"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2000.0871"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gep.2007.12.005"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200805048"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00798.x"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21776"}],"container-title":["Journal of Comparative Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcne.23547","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cne.23547","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cne.23547","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cne.23547","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T09:16:24Z","timestamp":1696583784000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cne.23547"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,12]]},"references-count":64,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["10.1002\/cne.23547"],"URL":"https:\/\/doi.org\/10.1002\/cne.23547","archive":["Portico"],"relation":{},"ISSN":["0021-9967","1096-9861"],"issn-type":[{"value":"0021-9967","type":"print"},{"value":"1096-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,12]]}}}