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A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation‐contraction coupling in the mouse heart
dc.contributor.authorNoujaim, Sami F.
dc.contributor.authorKaur, Kuljeet
dc.contributor.authorMilstein, Michelle
dc.contributor.authorJones, Julie M.
dc.contributor.authorFurspan, Philip
dc.contributor.authorJiang, Daniel
dc.contributor.authorAuerbach, David S.
dc.contributor.authorHerron, Todd
dc.contributor.authorMeisler, Miriam H.
dc.contributor.authorJalife, José
dc.date.accessioned2020-03-17T18:35:09Z
dc.date.available2020-03-17T18:35:09Z
dc.date.issued2012-01
dc.identifier.citationNoujaim, Sami F.; Kaur, Kuljeet; Milstein, Michelle; Jones, Julie M.; Furspan, Philip; Jiang, Daniel; Auerbach, David S.; Herron, Todd; Meisler, Miriam H.; Jalife, José (2012). "A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation‐contraction coupling in the mouse heart." The FASEB Journal 26(1): 63-72.
dc.identifier.issn0892-6638
dc.identifier.issn1530-6860
dc.identifier.urihttps://hdl.handle.net/2027.42/154524
dc.description.abstractEvidence supports the expression of brain‐type sodium channels in the heart. Their functional role, however, remains controversial. We used global NaV1.6‐null mice to test the hypothesis that NaV1.6 contributes to the maintenance of propagation in the myocardium and to excitation‐contraction (EC) coupling. We demonstrated expression of transcripts encoding full‐length NaV1.6 in isolated ventricular myocytes and confirmed the striated pattern of NaV1.6 fluorescence in myocytes. On the ECG, the PR and QRS intervals were prolonged in the null mice, and the Ca2+ transients were longer in the null cells. Under patch clamping, at holding potential (HP) = –120 mV, the peak INa was similar in both phenotypes. However, at HP = –70 mV, the peak INa was smaller in the nulls. In optical mapping, at 4 mM [K+]o, 17 null hearts showed slight (7%) reduction of ventricular conduction velocity (CV) compared to 16 wild‐type hearts. At 12 mM [K+]o, CV was 25% slower in a subset of 9 null vs. 9 wild‐type hearts. These results highlight the importance of neuronal sodium channels in the heart, whereby NaV1.6 participates in EC coupling, and represents an intrinsic depolarizing reserve that contributes to excitation.—Noujaim, S. F., Kaur, K., Milstein, M., Jones, J. M., Furspan, P., Jiang, D., Auerbach, D. S., Herron, T., Meisler, M. H., Jalife, J. A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation‐contraction coupling in the mouse heart. FASEB J. 26, 63–72 (2012). www.fasebj.org
dc.publisherWiley Periodicals, Inc.
dc.subject.otherataxia3
dc.subject.otheroptical mapping
dc.subject.otherKey Words
dc.subject.otherhyperkalemia
dc.subject.otherbrain‐type sodium channels
dc.titleA null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation‐contraction coupling in the mouse heart
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelBiology
dc.subject.hlbtoplevelScience
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/154524/1/fsb2fj10179770.pdf
dc.identifier.doi10.1096/fj.10-179770
dc.identifier.sourceThe FASEB Journal
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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