A BIPHASIC ROLE FOR THE VOLTAGE-GATED SODIUM CHANNEL SCN5LAB IN CARDIAC DEVELOPMENT OF ZEBRAFISH
JEFFREY S. BENNETT
Dissertation under direction of Professor Dan M. Roden, M.D.
Voltage-gated sodium channels (VGSCs) play an important role in generation and propagation of action potentials in nervous and cardiac tissues. Less is known of a possible role for them in development of the heart. Homozygous deletion of the voltage-gated sodium channel Scn5a results in embryonic lethality and developmental defects in the mouse heart. Morpholino knockdown of the two cardiac VGSC isoforms in zebrafish, scn5Laa and scn5Lab, results in small dysmorphic ventricles and death by four days post-fertilization.
Here, I examine a role for scn5Lab in multiple phases of cardiac development. I find that loss of scn5Lab results in impaired specification of pre-cardiac mesoderm, with specific loss of the cardiac transcription nkx2.5. Differentiation of myocardium from the second heart field is determined to be intact, genetically and morphologically. Further I find that proliferation of differentiated cardiomyocytes is absent in morpholino-injected embryos, an effect that appears to be independent of impaired cardiac function. Electrophysiologic studies suggest voltage-gated sodium channels are present, but not required for action potentials at this time. I conclude that scn5Lab has a biphasic role in cardiac development of zebrafish, likely independent of its role in sodium ion permeation
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-06172013-124441 |
| Date | 17 June 2013 |
| Creators | Bennett, Jeffrey Scott |
| Contributors | H. Scott Baldwin, Charles Hong, Al George, Doug Mortlock, Dan Roden |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-06172013-124441/ |
| Rights | restrictone, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
Page generated in 0.0715 seconds