Two heterozygous Cav3.2 channel mutations in a pediatric chronic pain patient: recording condition-dependent biophysical effects

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dc.contributor.authorSouza, Ivana Assis
dc.contributor.authorGandini, María Alejandra
dc.contributor.authorWan, Miranda M.
dc.contributor.authorZamponi, Gerald W.
dc.date.accessioned2018-05-30T16:59:00Z
dc.date.available2018-05-30T16:59:00Z
dc.date.issued2016-12-26
dc.description.abstractWe report expression system-dependent effects of heterozygous mutations (P769L and A1059S) in the Cav3.2 CACNA1H gene identified in a pediatric patient with chronic pain and absence seizures. The mutations were introduced individually into recombinant channels and then analyzed by means of electrophysiology. When both mutants were co-expressed in tsA-201 cells, we observed a loss of channel function, with significantly smaller current densities across a wide range of voltages (-40 to +20 mV). In addition, when both mutant channels were co-expressed, the channels opened at a more depolarizing potential with a ~5-mV right shift in the half-activation potential, with no changes in half-inactivation potential and the rate of recovery from inactivation. Interestingly, when both mutants were co-expressed in the neuronal-derived CAD cells in a different extracellular milieu, the effect was remarkably different. Although not statistically significant (p < 0.07), current densities appeared augmented compared to wild-type channels and the difference in the half-activation potential was lost. This could be attributed to the replacement of extracellular sodium and potassium with tetraethylammonium chloride. Our results show that experimental conditions can be a confounding factor in the biophysical effects of T-type calcium channel mutations found in certain neurological disorders.en_US
dc.identifier.citationSouza, I. A., Gandini, M. A., Wan, M. M., & Zamponi, G. W. (2016). Two heterozygous Cav3.2 channel mutations in a pediatric chronic pain patient: recording condition-dependent biophysical effects. Pflugers Archiv European Journal of Physiology, 468(4), 635–642. https://doi.org/10.1007/s00424-015-1776-3en_US
dc.identifier.doihttp://dx.doi.org/10.1007/s00424-015-1776-3en_US
dc.identifier.urihttp://hdl.handle.net/1880/106715
dc.identifier.urihttps://doi.org/10.11575/PRISM/43821
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.publisher.departmentPhysiology & Pharmacologyen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.policyhttps://www.elsevier.com/about/our-business/policies/sharingen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleTwo heterozygous Cav3.2 channel mutations in a pediatric chronic pain patient: recording condition-dependent biophysical effectsen_US
dc.typejournal articleen_US
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