A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation‐contraction coupling in the mouse heart
dc.contributor.author | Noujaim, Sami F. | |
dc.contributor.author | Kaur, Kuljeet | |
dc.contributor.author | Milstein, Michelle | |
dc.contributor.author | Jones, Julie M. | |
dc.contributor.author | Furspan, Philip | |
dc.contributor.author | Jiang, Daniel | |
dc.contributor.author | Auerbach, David S. | |
dc.contributor.author | Herron, Todd | |
dc.contributor.author | Meisler, Miriam H. | |
dc.contributor.author | Jalife, José | |
dc.date.accessioned | 2020-03-17T18:35:09Z | |
dc.date.available | 2020-03-17T18:35:09Z | |
dc.date.issued | 2012-01 | |
dc.identifier.citation | Noujaim, 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.issn | 0892-6638 | |
dc.identifier.issn | 1530-6860 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/154524 | |
dc.description.abstract | Evidence 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.publisher | Wiley Periodicals, Inc. | |
dc.subject.other | ataxia3 | |
dc.subject.other | optical mapping | |
dc.subject.other | Key Words | |
dc.subject.other | hyperkalemia | |
dc.subject.other | brain‐type sodium channels | |
dc.title | A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation‐contraction coupling in the mouse heart | |
dc.type | Article | |
dc.rights.robots | IndexNoFollow | |
dc.subject.hlbsecondlevel | Biology | |
dc.subject.hlbtoplevel | Science | |
dc.description.peerreviewed | Peer Reviewed | |
dc.description.bitstreamurl | https://deepblue.lib.umich.edu/bitstream/2027.42/154524/1/fsb2fj10179770.pdf | |
dc.identifier.doi | 10.1096/fj.10-179770 | |
dc.identifier.source | The FASEB Journal | |
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dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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