{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:43:04Z","timestamp":1791276184009,"version":"4.1.0"},"reference-count":77,"publisher":"The Company of Biologists","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,11,1]]},"abstract":"<jats:p>Several human diseases, including hypokalemic periodic paralysis and Timothy syndrome, are caused by mutations in voltage-gated calcium channels. The effects of these mutations are not always well understood, partially because of difficulties in expressing these channels in heterologous systems. The use of Caenorhabditis elegans could be an alternative approach to determine the effects of mutations on voltage-gated calcium channel function because all the main types of voltage-gated calcium channels are found in C. elegans, a large panel of mutations already exists and efficient genetic tools are available to engineer customized mutations in any gene. In this study, we characterize the effects of two gain-of-function mutations in egl-19, which encodes the L-type calcium channel \u03b11 subunit. One of these mutations, ad695, leads to the replacement of a hydrophobic residue in the IIIS4 segment. The other mutation, n2368, changes a conserved glycine of IS6 segment; this mutation has been identified in patients with Timothy syndrome. We show that both egl-19 (gain-of-function) mutants have defects in locomotion and morphology that are linked to higher muscle tone. Using in situ electrophysiological approaches in striated muscle cells, we provide evidence that this high muscle tone is due to a shift of the voltage dependency towards negative potentials, associated with a decrease of the inactivation rate of the L-type Ca2+ current. Moreover, we show that the maximal conductance of the Ca2+ current is decreased in the strongest mutant egl-19(n2368), and that this decrease is correlated with a mislocalization of the channel.<\/jats:p>","DOI":"10.1242\/jeb.106732","type":"journal-article","created":{"date-parts":[[2014,9,11]],"date-time":"2014-09-11T21:43:06Z","timestamp":1410471786000},"page":"3805-3814","source":"Crossref","is-referenced-by-count":19,"title":["Hyperactivation of L-type voltage-gated Ca2+ channels in\n                    <i>Caenorhabditis elegans<\/i>\n                    striated muscle can result from point mutations in the IS6 or the IIIS4 segment of the \u03b11 subunit"],"prefix":"10.1242","volume":"217","author":[{"given":"Viviane","family":"Lain\u00e9","sequence":"first","affiliation":[{"name":"CNRS, UMR 5534, Universit\u00e9 Lyon 1 , Villeurbanne, F-69622 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Rony","family":"S\u00e9gor","sequence":"additional","affiliation":[{"name":"CNRS, UMR 5534, Universit\u00e9 Lyon 1 , Villeurbanne, F-69622 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhan","sequence":"additional","affiliation":[{"name":"CNRS, UMR 5534, Universit\u00e9 Lyon 1 , Villeurbanne, F-69622 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Bessereau","sequence":"additional","affiliation":[{"name":"CNRS, UMR 5534, Universit\u00e9 Lyon 1 , Villeurbanne, F-69622 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maelle","family":"Jospin","sequence":"additional","affiliation":[{"name":"CNRS, UMR 5534, Universit\u00e9 Lyon 1 , Villeurbanne, F-69622 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2025112706575552600_R1","doi-asserted-by":"crossref","first-page":"7602","DOI":"10.1523\/JNEUROSCI.5727-11.2012","article-title":"The role of a voltage-dependent Ca2+ channel intracellular linker: a structure\u2013function analysis","volume":"32","author":"Almagor","year":"2012","journal-title":"J. Neurosci."},{"key":"2025112706575552600_R2","doi-asserted-by":"crossref","first-page":"3907","DOI":"10.1016\/j.febslet.2005.06.008","article-title":"Transfer of \u03b2 subunit regulation from high to low voltage-gated Ca2+ channels","volume":"579","author":"Arias","year":"2005","journal-title":"FEBS Lett."},{"key":"2025112706575552600_R3","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1073\/pnas.87.1.323","article-title":"A neutral amino acid change in segment IIS4 dramatically alters the gating properties of the voltage-dependent sodium channel","volume":"87","author":"Auld","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025112706575552600_R4","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1073\/pnas.0710501105","article-title":"The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels","volume":"105","author":"Barrett","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025112706575552600_R5","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1749-8104-2-24","article-title":"Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans","volume":"2","author":"Bauer Huang","year":"2007","journal-title":"Neural Dev."},{"key":"2025112706575552600_R6","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.bbamem.2007.03.002","article-title":"Role of hydrophobic residues in the voltage sensors of the voltage-gated sodium channel","volume":"1768","author":"Bendahhou","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"2025112706575552600_R7","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1074\/jbc.M609153200","article-title":"Probing the architecture of an L-type calcium channel with a charged phenylalkylamine: evidence for a widely open pore and drug trapping","volume":"282","author":"Beyl","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2025112706575552600_R8","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","article-title":"The genetics of Caenorhabditis elegans","volume":"77","author":"Brenner","year":"1974","journal-title":"Genetics"},{"key":"2025112706575552600_R9","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/1471-2350-10-104","article-title":"The role of CACNA1S in predisposition to malignant hyperthermia","volume":"10","author":"Carpenter","year":"2009","journal-title":"BMC Med. Genet."},{"key":"2025112706575552600_R10","doi-asserted-by":"crossref","first-page":"8979","DOI":"10.1073\/pnas.1403731111","article-title":"Functional exofacially tagged N-type calcium channels elucidate the interaction with auxiliary \u03b12\u03b4-1 subunits","volume":"111","author":"Cassidy","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025112706575552600_R11","doi-asserted-by":"crossref","first-page":"a003947","DOI":"10.1101\/cshperspect.a003947","article-title":"Voltage-gated calcium channels","volume":"3","author":"Catterall","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2025112706575552600_R12","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00424-008-0534-1","article-title":"Introduction into Ca(v)2.1 of the homologous mutation of Ca(v)1.2 causing the Timothy syndrome questions the role of V421 in the phenotypic definition of P-type Ca2+ channel","volume":"457","author":"Cens","year":"2008","journal-title":"Pflugers Arch."},{"key":"2025112706575552600_R13","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1136\/jmg.2008.059766","article-title":"Early onset of hypokalaemic periodic paralysis caused by a novel mutation of the CACNA1S gene","volume":"45","author":"Chabrier","year":"2008","journal-title":"J. Med. Genet."},{"key":"2025112706575552600_R14","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1161\/CIRCRESAHA.111.248252","article-title":"Restoration of normal L-type Ca2+ channel function during Timothy syndrome by ablation of an anchoring protein","volume":"109","author":"Cheng","year":"2011","journal-title":"Circ. Res."},{"key":"2025112706575552600_R15","first-page":"pe34","article-title":"L-type calcium channels: on the fast track to nuclear signaling","volume":"5","author":"D'Arco","year":"2012","journal-title":"Sci. Signal."},{"key":"2025112706575552600_R16","doi-asserted-by":"crossref","first-page":"31557","DOI":"10.1074\/jbc.M111.255273","article-title":"Timothy mutation disrupts the link between activation and inactivation in Ca(V)1.2 protein","volume":"286","author":"Depil","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2025112706575552600_R17","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3109\/09687688.2012.710343","article-title":"Role of hydrophobic and ionic forces in the movement of S4 of the Shaker potassium channel","volume":"29","author":"Elliott","year":"2012","journal-title":"Mol. Membr. Biol."},{"key":"2025112706575552600_R18","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1073\/pnas.0511322103","article-title":"Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices","volume":"103","author":"Erxleben","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025112706575552600_R19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1085\/jgp.200810143","article-title":"Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation","volume":"133","author":"Findeisen","year":"2009","journal-title":"J. Gen. Physiol."},{"key":"2025112706575552600_R20","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng0394-267","article-title":"Mapping of the hypokalaemic periodic paralysis (HypoPP) locus to chromosome 1q31-32 in three European families","volume":"6","author":"Fontaine","year":"1994","journal-title":"Nat. Genet."},{"key":"2025112706575552600_R21","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1002\/neu.20261","article-title":"Effects of voltage-gated calcium channel subunit genes on calcium influx in cultured C. elegans mechanosensory neurons","volume":"66","author":"Fr\u00f8kjaer-Jensen","year":"2006","journal-title":"J. Neurobiol."},{"key":"2025112706575552600_R22","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1038\/ng.248","article-title":"Single-copy insertion of transgenes in Caenorhabditis elegans","volume":"40","author":"Fr\u00f8kjaer-Jensen","year":"2008","journal-title":"Nat. Genet."},{"key":"2025112706575552600_R23","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1073\/pnas.1012346108","article-title":"Action potentials drive body wall muscle contractions in Caenorhabditis elegans","volume":"108","author":"Gao","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025112706575552600_R24","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1016\/S0006-3495(97)78896-9","article-title":"Role of S4 segments and the leucine heptad motif in the activation of an L-type calcium channel","volume":"72","author":"Garc\u00eda","year":"1997","journal-title":"Biophys. J."},{"key":"2025112706575552600_R25","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.cell.2006.10.017","article-title":"The C terminus of the L-type voltage-gated calcium channel Ca(V)1.2 encodes a transcription factor","volume":"127","author":"Gomez-Ospina","year":"2006","journal-title":"Cell"},{"key":"2025112706575552600_R26","doi-asserted-by":"crossref","first-page":"42","DOI":"10.4161\/chan.4.1.10562","article-title":"Swapping the I\u2013II intracellular linker between L-type CaV1.2 and R-type CaV2.3 high-voltage gated calcium channels exchanges activation attributes","volume":"4","author":"Gonzalez-Gutierrez","year":"2010","journal-title":"Channels"},{"key":"2025112706575552600_R27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jns.2011.07.046","article-title":"A novel mutation in the calcium channel gene in a family with hypokalemic periodic paralysis","volume":"309","author":"Hirano","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"2025112706575552600_R28","doi-asserted-by":"crossref","first-page":"38471","DOI":"10.1074\/jbc.M507013200","article-title":"Structural determinants of L-type channel activation in segment IIS6 revealed by a retinal disorder","volume":"280","author":"Hohaus","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2025112706575552600_R29","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1083\/jcb.200203055","article-title":"The L-type voltage-dependent Ca2+ channel EGL-19 controls body wall muscle function in Caenorhabditis elegans","volume":"159","author":"Jospin","year":"2002","journal-title":"J. Cell Biol."},{"key":"2025112706575552600_R30","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1093\/hmg\/3.8.1415","article-title":"A calcium channel mutation causing hypokalemic periodic paralysis","volume":"3","author":"Jurkat-Rott","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"2025112706575552600_R31","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/jhg.2009.92","article-title":"Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a South American family","volume":"54","author":"Ke","year":"2009","journal-title":"J. Hum. Genet."},{"key":"2025112706575552600_R32","doi-asserted-by":"crossref","first-page":"15555","DOI":"10.1016\/S0021-9258(18)98436-X","article-title":"Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases","volume":"266","author":"Kennelly","year":"1991","journal-title":"J. Biol. Chem."},{"key":"2025112706575552600_R33","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S0896-6273(00)81196-4","article-title":"Optical imaging of calcium transients in neurons and pharyngeal muscle of C. elegans","volume":"26","author":"Kerr","year":"2000","journal-title":"Neuron"},{"key":"2025112706575552600_R34","doi-asserted-by":"crossref","first-page":"e1000780","DOI":"10.1371\/journal.pgen.1000780","article-title":"The dystrophin complex controls BK channel localization and muscle activity in Caenorhabditis elegans","volume":"5","author":"Kim","year":"2009","journal-title":"PLoS Genet."},{"key":"2025112706575552600_R35","doi-asserted-by":"crossref","first-page":"12276","DOI":"10.1074\/jbc.M808402200","article-title":"Coupled and independent contributions of residues in IS6 and IIS6 to activation gating of CaV1.2","volume":"284","author":"Kudrnac","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2025112706575552600_R36","doi-asserted-by":"crossref","first-page":"36180","DOI":"10.1074\/jbc.M111.256149","article-title":"The \u03b11 subunit EGL-19, the \u03b12\/\u03b4 subunit UNC-36, and the \u03b2 subunit CCB-1 underlie voltage-dependent calcium currents in Caenorhabditis elegans striated muscle","volume":"286","author":"Lain\u00e9","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2025112706575552600_R37","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10974-007-9104-y","article-title":"The C. elegans dense body: anchoring and signaling structure of the muscle","volume":"28","author":"Lecroisey","year":"2007","journal-title":"J. Muscle Res. Cell Motil."},{"key":"2025112706575552600_R38","doi-asserted-by":"crossref","first-page":"6066","DOI":"10.1093\/emboj\/16.20.6066","article-title":"Mutations in the \u03b11 subunit of an L-type voltage-activated Ca2+ channel cause myotonia in Caenorhabditis elegans","volume":"16","author":"Lee","year":"1997","journal-title":"EMBO J."},{"key":"2025112706575552600_R39","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s12031-011-9596-1","article-title":"A novel mutation in CACNA1S gene associated with hypokalemic periodic paralysis which has a gender difference in the penetrance","volume":"46","author":"Li","year":"2012","journal-title":"J. Mol. Neurosci."},{"key":"2025112706575552600_R40","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1113\/jphysiol.2010.200683","article-title":"Genetic dissection of ion currents underlying all-or-none action potentials in C. elegans body-wall muscle cells","volume":"589","author":"Liu","year":"2011","journal-title":"J. Physiol."},{"key":"2025112706575552600_R41","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1038\/ncomms2925","article-title":"Postsynaptic current bursts instruct action potential firing at a graded synapse","volume":"4","author":"Liu","year":"2013","journal-title":"Nat. Commun."},{"key":"2025112706575552600_R42","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1126\/science.1116269","article-title":"Crystal structure of a mammalian voltage-dependent Shaker family K+ channel","volume":"309","author":"Long","year":"2005","journal-title":"Science"},{"key":"2025112706575552600_R43","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature06265","article-title":"Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment","volume":"450","author":"Long","year":"2007","journal-title":"Nature"},{"key":"2025112706575552600_R44","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0896-6273(91)90271-Z","article-title":"Hydrophobic substitution mutations in the S4 sequence alter voltage-dependent gating in Shaker K+ channels","volume":"7","author":"Lopez","year":"1991","journal-title":"Neuron"},{"key":"2025112706575552600_R45","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1083\/jcb.134.4.885","article-title":"unc-68 encodes a ryanodine receptor involved in regulating C. elegans body-wall muscle contraction","volume":"134","author":"Maryon","year":"1996","journal-title":"J. Cell Biol."},{"key":"2025112706575552600_R46","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1073\/pnas.88.7.2931","article-title":"A role for hydrophobic residues in the voltage-dependent gating of Shaker K+ channels","volume":"88","author":"McCormack","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025112706575552600_R47","doi-asserted-by":"crossref","first-page":"12593","DOI":"10.1073\/pnas.93.22.12593","article-title":"A genetic selection for Caenorhabditis elegans synaptic transmission mutants","volume":"93","author":"Miller","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025112706575552600_R48","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.1242\/dev.00670","article-title":"Modulation of EGF receptor-mediated vulva development by the heterotrimeric G-protein G\u03b1q and excitable cells in C. elegans","volume":"130","author":"Moghal","year":"2003","journal-title":"Development"},{"key":"2025112706575552600_R49","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1086\/515454","article-title":"Malignant-hyperthermia susceptibility is associated with a mutation of the \u03b11-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle","volume":"60","author":"Monnier","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"2025112706575552600_R50","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/312121a0","article-title":"Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence","volume":"312","author":"Noda","year":"1984","journal-title":"Nature"},{"key":"2025112706575552600_R51","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0896-6273(04)00250-8","article-title":"Structural analysis of the voltage-dependent calcium channel \u03b2 subunit functional core and its complex with the \u03b11 interaction domain","volume":"42","author":"Opatowsky","year":"2004","journal-title":"Neuron"},{"key":"2025112706575552600_R52","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1085\/jgp.201310975","article-title":"Hydrophobic interactions between the voltage sensor and pore mediate inactivation in Kv11.1 channels","volume":"142","author":"Perry","year":"2013","journal-title":"J. Gen. Physiol."},{"key":"2025112706575552600_R53","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1016\/j.bpj.2011.02.035","article-title":"Caenorhabditis elegans body mechanics are regulated by body wall muscle tone","volume":"100","author":"Petzold","year":"2011","journal-title":"Biophys. J."},{"key":"2025112706575552600_R54","doi-asserted-by":"crossref","first-page":"C1345","DOI":"10.1152\/ajpcell.00008.2010","article-title":"Identification and functional characterization of malignant hyperthermia mutation T1354S in the outer pore of the Cav\u03b11S-subunit","volume":"299","author":"Pirone","year":"2010","journal-title":"Am. J. Physiol."},{"key":"2025112706575552600_R55","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/368067a0","article-title":"Calcium channel \u03b2-subunit binds to a conserved motif in the I\u2013II cytoplasmic linker of the \u03b1 1-subunit","volume":"368","author":"Pragnell","year":"1994","journal-title":"Nature"},{"key":"2025112706575552600_R56","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/0092-8674(94)90135-X","article-title":"Dihydropyridine receptor mutations cause hypokalemic periodic paralysis","volume":"77","author":"Pt\u00e1cek","year":"1994","journal-title":"Cell"},{"key":"2025112706575552600_R57","doi-asserted-by":"crossref","first-page":"39424","DOI":"10.1074\/jbc.M607405200","article-title":"The role of the GX9GX3G motif in the gating of high voltage-activated Ca2+ channels","volume":"281","author":"Raybaud","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2025112706575552600_R58","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1038\/nn.2383","article-title":"Presynaptic CaV2 calcium channel traffic requires CALF-1 and the \u03b1(2)\u03b4 subunit UNC-36","volume":"12","author":"Saheki","year":"2009","journal-title":"Nat. Neurosci."},{"key":"2025112706575552600_R59","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1161\/CIRCRESAHA.108.191387","article-title":"L-type calcium channel C-terminus autoregulates transcription","volume":"104","author":"Schroder","year":"2009","journal-title":"Circ. Res."},{"key":"2025112706575552600_R60","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1242\/jeb.01615","article-title":"CCA-1, EGL-19 and EXP-2 currents shape action potentials in the Caenorhabditis elegans pharynx","volume":"208","author":"Shtonda","year":"2005","journal-title":"J. Exp. Biol."},{"key":"2025112706575552600_R61","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.neuron.2005.06.012","article-title":"Ion permeation through a voltage-sensitive gating pore in brain sodium channels having voltage sensor mutations","volume":"47","author":"Sokolov","year":"2005","journal-title":"Neuron"},{"key":"2025112706575552600_R62","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cell.2004.09.011","article-title":"Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism","volume":"119","author":"Splawski","year":"2004","journal-title":"Cell"},{"key":"2025112706575552600_R63","doi-asserted-by":"crossref","first-page":"8089","DOI":"10.1073\/pnas.0502506102","article-title":"Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations","volume":"102","author":"Splawski","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025112706575552600_R64","doi-asserted-by":"crossref","first-page":"e40182","DOI":"10.1371\/journal.pone.0040182","article-title":"Large isoforms of UNC-89 (obscurin) are required for muscle cell architecture and optimal calcium release in Caenorhabditis elegans","volume":"7","author":"Spooner","year":"2012","journal-title":"PLoS ONE"},{"key":"2025112706575552600_R65","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nature02270","article-title":"A proton pore in a potassium channel voltage sensor reveals a focused electric field","volume":"427","author":"Starace","year":"2004","journal-title":"Nature"},{"key":"2025112706575552600_R66","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/339597a0","article-title":"Structural parts involved in activation and inactivation of the sodium channel","volume":"339","author":"St\u00fchmer","year":"1989","journal-title":"Nature"},{"key":"2025112706575552600_R67","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1006\/dbio.2000.9854","article-title":"Voltage-gated calcium channels direct neuronal migration in Caenorhabditis elegans","volume":"226","author":"Tam","year":"2000","journal-title":"Dev. Biol."},{"key":"2025112706575552600_R68","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.neuron.2004.12.047","article-title":"Voltage-sensing arginines in a potassium channel permeate and occlude cation-selective pores","volume":"45","author":"Tombola","year":"2005","journal-title":"Neuron"},{"key":"2025112706575552600_R69","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s12630-010-9314-4","article-title":"A report of fulminant malignant hyperthermia in a patient with a novel mutation of the CACNA1S gene","volume":"57","author":"Toppin","year":"2010","journal-title":"Can. J. Anaesth."},{"key":"2025112706575552600_R70","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nature02588","article-title":"Structure of a complex between a voltage-gated calcium channel \u03b2-subunit and an \u03b1-subunit domain","volume":"429","author":"Van Petegem","year":"2004","journal-title":"Nature"},{"key":"2025112706575552600_R71","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00109-005-0638-4","article-title":"Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family","volume":"83","author":"Wang","year":"2005","journal-title":"J. Mol. Med."},{"key":"2025112706575552600_R72","doi-asserted-by":"crossref","first-page":"4580","DOI":"10.1172\/JCI66091","article-title":"A calcium channel mutant mouse model of hypokalemic periodic paralysis","volume":"122","author":"Wu","year":"2012","journal-title":"J. Clin. 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