Bradley M. Palmer, Ph.D.
Dr. Palmer received his Ph.D. in Bioengineering from The Pennsylvania State University in Hershey, PA, and obtained postdoctoral training at The University of Vermont. Dr. Palmer joined the faculty of the University of Vermont in 2009.
My lab focuses on examining contraction and relaxation function in cardiac muscle. While contraction function is clearly important for the heart to effectively drive blood through the vasculature, relaxation function is just as important to assure filling of the heart chambers with plenty of blood. We apply several different techniques to examine the influence of calcium regulation and myofilament performance in cardiac muscle function, and we apply these techniques to various muscle systems including insect flight muscle, isolated cardiac myocytes and cardiac biopsy samples taken from patients undergoing cardiothoracic surgery.
Zinc, Zinc and Still More Zinc
Zinc content in the serum and/or heart is abnormally low in humans with heart failure or other conditions such as diabetes, hypertension, coronary artery disease or myocardial infarction. Amazingly, cardiac zinc content positively correlates with ejection fraction in humans with coronary artery disease (r=0.428, P<0.05; Oster et al. Eur Heart J. 1993). Elevated cardiac zinc status also preserves cardiac function in the face of oxidative stress associated with ischemia/reperfusion or diabetes. Zinc most likely provides cardioprotection and improves cardiac function through its effects on Ca2+ regulation, myofilament force-production and/or proximal second messengers. It has also been suggested that zinc can act as a messenger of gene expression.
Our laboratory focuses on the effects of cardiac zinc status on Ca2+ regulation, myofilament function and gene regulation.
Zinc and Calcium Regulation in Cardiac Myocytes
Through simultaneous detection of the intracellular concentrations of Zn2+ and Ca2+ in cardiac myocytes, we (namely Ting) are able to examine the interaction between Zn2+ and Ca2+ regulation in heart muscle. See the accompanying figure, which demonstrates how Zn2+ affects cardiomyocyte performance. Surprisingly little is known about cardiac myocyte regulation of Zn2+ or about its interaction with the Ca2+ regulation. Almost all that is known is that extracellular Zn2+ passes readily through the sarcolemmal L-type channel and competitively inhibits the inward Ca2+ current. Relaxation function after extracellular Zn2+ removal, however, remains enhanced and cannot be explained by effects on inward calcium current. It appears then that Zn2+ competes for or modulates the function of other Ca2+ regulatory proteins. We (Ting again) are testing the hypothesis that [Zn2+]int improves cardiac diastolic function by lowering Ca2+ load in the sarcoplasmic reticulum and/or enhancing Na+-dependent Ca2+ efflux, thus ultimately lowering total intracellular calcium content.
Palmer BM, Olsson MC, Lynch JM, Mace LC, Snyder SM, Valent S, Moore RL (1999) Chronic run training suppresses α-adrenergic response of rat cardiomyocytes and isovolumic left ventricle. Am J Physiol Heart Circ Physiol 277(6): H2136-H2144.
Palmer TB, Agu-Udemba CC, Palmer BM (2018) Acute effects of static stretching on passive stiffness and postural balance in healthy, elderly men. Phys Sportsmed 46(1): 78-86.
Runte KE, Bell SP, Selby DE, Häußler TN, Ashikaga T, LeWinter MM, Palmer BM, Meyer M (2017) Relaxation and the Role of Calcium in Isolated Contracting Myocardium From Patients With Hypertensive Heart Disease and Heart Failure With Preserved Ejection Fraction. Circ Heart Fail 10(8): .
Helmes M, Najafi A, Palmer BM, Breel E, Rijnveld N, Iannuzzi D, van der Velden J (2016) Mimicking the cardiac cycle in intact cardiomyocytes using diastolic and systolic force clamps; measuring power output. Cardiovasc Res 111(1): 66-73.
LeWinter MM, Palmer BM (2015) Updating the physiology and pathophysiology of cardiac Myosin-binding protein-C. Circ Heart Fail 8(3): 417-21.
Tewari SG, Bugenhagen SM, Palmer BM, Beard DA (2016) Dynamics of cross-bridge cycling, ATP hydrolysis, force generation, and deformation in cardiac muscle. J Mol Cell Cardiol 96: 11-25.
Zile MR, Baicu CF, Ikonomidis JS, Stroud RE, Nietert PJ, Bradshaw AD, Slater R, Palmer BM, Van Buren P, Meyer M, Redfield MM, Bull DA, Granzier HL, LeWinter MM (2015) Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin. Circulation 131(14): 1247-59.
Faculty Highlighted Publications
Selby DE, Palmer BM, LeWinter MM, Meyer M. Tachycardia-induced diastolic dysfunction and resting tone in myocardium from patients with a normal ejection fraction. J. Am. Coll. Cardiol. 2011. 58(2):147-154.
Toth MJ, Miller MS, VanBuren P, Bedrin NG, LeWinter MM, Ades PA, Palmer BM. Resistance training alters skeletal muscle structure and function in human heart failure: effects at the tissue, cellular and molecular levels. J Physiol. 2012 Mar 1;590(Pt 5):1243-59. PubMed PMID: 22199163.
Palmer BM, Wang Y, Miller MS. Distribution of myosin attachment times predicted from viscoelastic mechanics of striated muscle. J Biomed Biotechnol. 2011;2011:592343. Epub 2011 Nov 17. PubMed PMID: 22190855; PubMed Central PMCID: PMC3228685.
Hefer D, Yi T, Selby DE, Fishbaugher DE, Tremble SM, Begin KJ, Gogo P, Lewinter MM, Meyer M, Palmer BM, Vanburen P. Erythropoietin induces positive inotropic and lusitropic effects in murine and human myocardium. J Mol Cell Cardiol. 2012 Jan;52(1):256-63. Epub 2011 Oct 14. PubMed PMID: 22062955; PubMed Central PMCID: PMC3250092.
Palmer BM, Sadayappan S, Wang Y, Weith AE, Previs MJ, Bekyarova T, Irving TC, Robbins J, Maughan DW. Roles for cardiac MyBP-C in maintaining myofilament lattice rigidity and prolonging myosin cross-bridge lifetime. Biophys J. 2011 Oct 5;101(7):1661-9. PubMed PMID: 21961592; PubMed Central PMCID: PMC3183797.