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However, functional assessment of HypoPP mutant channels has been hampered by difficulties in achieving sufficient plasma membrane expression in cells that are not of muscle origin. In this study, we show that coexpression of Stac3 dramatically increases the expression of human CaV1.1 (plus \u03b12-\u03b41b and \u03b21a subunits) at the plasma membrane of Xenopus laevis oocytes. In voltage-clamp studies with the cut-open oocyte clamp, we observe ionic currents on the order of 1 \u03bcA and gating charge displacements of \u223c0.5\u20131 nC. Importantly, this high expression level is sufficient to ascertain whether HypoPP mutant channels are leaky because of missense mutations at arginine residues in S4 segments of the voltage sensor domains. We show that R528H and R528G in S4 of domain II both support gating pore currents, but unlike other R\/H HypoPP mutations, R528H does not conduct protons. Stac3-enhanced membrane expression of CaV1.1 in oocytes increases the throughput for functional studies of disease-associated mutations and is a new platform for investigating the voltage-dependent properties of CaV1.1 without the complexity of the transverse tubule network in skeletal muscle.<\/jats:p>","DOI":"10.1085\/jgp.201711962","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T14:56:18Z","timestamp":1517410578000},"page":"475-489","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Stac3 enhances expression of human CaV1.1 in <i>Xenopus<\/i> oocytes and reveals gating pore currents in HypoPP mutant channels"],"prefix":"10.1085","volume":"150","author":[{"given":"Fenfen","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0684-9705","authenticated-orcid":true,"given":"Marbella","family":"Quinonez","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9315-9429","authenticated-orcid":true,"given":"Marino","family":"DiFranco","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8428-3690","authenticated-orcid":true,"given":"Stephen C.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2018,1,31]]},"reference":[{"key":"2023072705012278700_bib1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.14302\/issn.2470-5020.jnrt-16-993","article-title":"Skeletal muscle calcium channel mutation R528G: enhanced channel inactivation and omega-current at hyperpolarization contribute to hypokalemic periodic paralysis","volume":"1","author":"Bednarz","year":"2016","journal-title":"Neurological Research and Therapy."},{"key":"2023072705012278700_bib2","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1113\/jphysiol.2010.186874","article-title":"Voltage-sensor mutations in channelopathies of skeletal muscle","volume":"588","author":"Cannon","year":"2010","journal-title":"J. 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