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Junctophilin Damage Contributes to Early Force Deficits and Excitation-Contraction Coupling Failure After Performing Eccentric Contractions

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Junctophilin Damage Contributes to Early Force Deficits and Excitation-Contraction Coupling Failure After Performing Eccentric Contractions Georgia State University ScholarWorks @ Georgia State University Kinesiology Dissertations Department of Kinesiology and Health 8-17-2009 Junctophilin Damage Contributes to Early Force Deficits and Excitation-Contraction Coupling Failure after Performing Eccentric Contractions Benjamin T. Corona Follow this and additional works at: https://scholarworks.gsu.edu/kin_health_diss Part of the Kinesiology Commons Recommended Citation Corona, Benjamin T., "Junctophilin Damage Contributes to Early Force Deficits and Excitation-Contraction Coupling Failure after Performing Eccentric Contractions." Dissertation, Georgia State University, 2009. https://scholarworks.gsu.edu/kin_health_diss/4 This Dissertation is brought to you for free and open access by the Department of Kinesiology and Health at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Kinesiology Dissertations by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. ACCEPTANCE This dissertation, JUNCTOPHILIN DAMAGE CONTRIBUTES TO EARLY FORCE DEFICITS AND EXCITATION-CONTRACTION COUPLING FAILURE AFTER PERFORMING ECCENTRIC CONTRACTIONS, by BENJAMIN T. CORONA, was prepared under the direction of the candidate’s Dissertation Advisory Committee. It is accepted by the committee members in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the College of Education, Georgia State University. The Dissertation Advisory Committee and the student’s Department Chair, as representatives of the faculty, certify that this dissertation has met all standards of excellence and scholarship as determined by the faculty. The Dean of the College of Education concurs. ______________________________ ______________________________ Christopher P. Ingalls, Ph.D. Jeffrey C. Rupp, Ph.D. Committee Chair Committee Member ______________________________ ______________________________ J. Andrew Doyle, Ph.D. Edward M. Balog, Ph.D. Committee Member Committee Member ______________________________ Date ______________________________ Jacalyn Lund, Ph.D. Chair, Department of Kinesiology and Health R. W. Kamphaus, Ph.D. Dean and Distinguished Researcher Professor College of Education AUTHOR’S STATEMENT By presenting this dissertation as a partial fulfillment of the requirements for the advanced degree from Georgia State University, I agree that the library of Georgia State University shall make it available for inspection and circulation in accordance with its regulations governing materials of this type. I agree that permission to quote, to copy from, or to publish this dissertation may be granted by the professor under whose direction it was written, by the College of Education’s director of graduate studies and research, or by me. Such quoting, copying, or publishing must be solely for scholarly purposes and will not involve potential financial gain. It is understood that any copying from or publication of this master’s thesis, which involves potential financial gain will not be allowed without my written permission. Benjamin T. Corona NOTICE TO BORROWERS All dissertations deposited in the Georgia State University library must be used in accordance with the stipulations prescribed by the author in the preceding statement. The author of this dissertation is: Benjamin T. Corona 2173 Collins Dr. Atlanta, GA 30318 The director of this dissertation is: Dr. Chrisotpher P. Ingalls, Ph.D. Department of Kinesiology and Health College of Education Georgia State University Atlanta, GA 30302-3975 VITA Benjamin T. Corona ADDRESS: 2173 Collins Drive Atlanta, GA 30318 EDUCATION: Ph.D. 2009 Georgia State University Sport Science M.S. 2006 Georgia State University Exercise Physiology B.S. 2003 University of Georgia Exercise Science PROFESSIONAL EXPERIENCE: 2005-Present Graduate Research Assistant Muscle Biology Laboratory Department of Kinesiology and Health Georgia State University, Atlanta, GA 2003-2005 Graduate Research Assistant Applied Physiology Laboratory Department of Kinesiology and Health Georgia State University PROFESSIONAL SOCIETIES AND ORGANIZATIONS: 2008-Present Atlanta Calcium Club, Georgia State University 2005-Present The American Physiological Society 2004-Present American College of Sports Medicine 2004-Present Southeast American College of Sports Medicine PUBLISHED PAPERS: Corona B.T., Rouviere C,. Hamilton S.L., Ingalls C.P. (2008). Eccentric contractions do not induce rhabdomyolysis in malignant hyperthermia susceptible mice. J Appl Physiol., 105:1542-1553. Corona B.T., Rouviere C,. Hamilton S.L., Ingalls C.P. (2008). FKBP12 Deficiency Reduces Strength Deficits After Eccentric Contraction-Induced Muscle Injury. J Appl Physiol., 105:527-537. Green M.S., Corona B.T., Doyle J.A,. Ingalls C.P. (2008). Carbohydrate-protein drinks do not enhance recovery from exercise-induced muscle injury. Int J Sport Nutr Exerc Metab., 18(1):1-18. PUBLISHED ABSTRACTS: Corona, B.T. & Ingalls, C.P. (2009). Malignant Hyperthermia Susceptible Mice Can Safely Perform Voluntary Endurance Training And Exhibit An Intrinsic Fatigue Resistance. Medicine & Science in Sports & Exercise. 41(5) Supplement: S593 (Abstract). Corona, B.T. & Ingalls, C.P. (2008). Nitric Oxide Synthase Inhibition Exacerbates Isolated EDL Muscle Force Deficits During and Immediately After Performing Eccentric Contractions. The Physiologist, 51(6): 76, Program #36.6. Corona, B.T., Wilson, A.K., Rouviere C., Hamilton, S.L., Ingalls, C.P. (2008). Changes in juctophilin 1 contribute to strength deficits after eccentric contraction-induced muscle injury. Experimental Biology 2008 Meeting Program. Abstract #962.35. Ingalls, C.P., B.T. Corona, Rouviere, C. (2008). Eccentric contractions protect skeletal muscle from temperature-induced contracture in Y522S RyR1 knockin mice. Experimental Biology 2008 Meeting Program. Abstract # 962.33. Ingalls, C.P., Corona, B.T., Rouviere, C., Hamilton, S.L. (2007). Effects of Eccentric Contractions on Skeletal Muscle Function in a Malignant Hyperthermia Mouse Model. Medicine & Science in Sports & Exercise. 39(5) Supplement: S432. Corona, B.T., Rouviere, C., Hamilton, S.L., Ingalls, C.P. (2007). Basic Skeletal Muscle Phenotype of a Knock-in Mouse Model of Malignant. Medicine & Science in Sports & Exercise. 39(5) Supplement: S431. PRESENTATIONS: Invited Presentations "Junctophilin And Strength Loss In Mouse Skeletal Muscle After Eccentric Contractions", Georgia State University, Department of Chemistry, Atlanta Calcium Club, May 20, 2009. “Does the Lack of “Junk” Cause Weakness after Exercise?”, Kinesiology and Health Spring Research Symposium, Georgia State University, April 8, 2009. “The Role of Ca2+ Dysregulation in Eccentric Contraction-Induced Muscle Injury”, Georgia State University, Department of Chemistry, Atlanta Calcium Club, June 17, 2008. ABSTRACT JUNCTOPHILIN DAMAGE CONTRIBUTES TO EARLY FORCE DEFICITS AND EXCITATION-CONTRACTION COUPLING FAILURE AFTER PERFORMING ECCENTRIC CONTRACTIONS by Benjamin T. Corona Junctophilins (JP1 & JP2) are expressed in skeletal muscle and are the primary proteins involved in transverse (T)-tubule and sarcoplasmic reticulum (SR) membrane apposition. During the performance of eccentric contractions, the apposition of T-tubule and SR membranes may be disrupted, resulting in excitation-contraction (EC) coupling failure and thus reduced force-producing capacity. In this study, we made three primary observations: 1) Through the first three days after the performance of 50 eccentric contractions in vivo by the left hindlimb anterior crural muscles of female mice, both JP1 and JP2 were significantly reduced by ~50 and 35%, respectively, while no reductions were observed after the performance of non-fatiguing concentric contractions; 2) following the performance of a repeated bout 50 eccentric contractions in vivo, only JP1 was immediately reduced (~30%) but recovered by 3d post-injury in tandem with the recovery of strength and EC coupling; and 3) following the performance of 10 eccentric contractions at either 15 or 35˚C by isolated mouse EDL muscle, isometric force, EC coupling, and JP1 and JP2 were only reduced after the 35˚C eccentric contractions. Regression analysis of JP1 and JP2 content in TA and EDL muscles from each set of experiments indicated that JP damage is significantly associated with early (0 – 3d) strength deficits after performing eccentric contractions (R = 0.49; P < 0.001). As a whole, the results of this study indicate that JP damage plays in role in early force deficits due to EC coupling failure following the performance of eccentric contractions. JUNCTOPHILIN DAMAGE CONTRIBUTES TO EARLY FORCE DEFICITS AND EXCITATION-CONTRACTION COUPLING FAILURE AFTER PERFORMING ECCENTRIC CONTRACTIONS by Benjamin T. Corona A Dissertation Presented in Partial Fulfillment of Requirements for the Degree of Doctor of Philosophy in Sport Science in the Department of Kinesiology and Health in the College of Education Georgia State University Atlanta, GA 2009 Copyright by Benjamin T. Corona 2009 ACKNOWLEDGEMENTS Allyson, my wife, whom I love and cherish, has made countless sacrifices for my studies and for that I am deeply grateful. My mom and dad have supported me in numerous ways throughout my education. Without them, earning this degree would have been remarkably more difficult. I cannot aptly express how wonderful it is to know that I have their love and support, always. I would like to thank my sister and her family, my brother, and my grandparents for their
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