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Distinguished University Professor and Head
Physiology and Biophysics
Molecular, Structural, and Integrated Cellular Biology of Cardiac Muscle Contraction in Health and Disease
W e want to know the fundamental mechanisms responsible for regulation of the molecular motors of heart muscle cells. These motors are housed in myofilaments responsible for shortening of cardiac muscle cells. Our focus is on the molecular switch that turns on the motor. Our experiments address the following question: What events signal switch function and how is the switch modulated by myofilament structure, chemistry, mechanical state and drugs? We approach this question at several levels of organization by integrating information derived from techniques using the disciplines of biophysics, biochemistry as well as molecular, structural and cellular biology. Acquired heart failure, and the linkage of sudden death in the young to mutations in sarcomeric proteins forms the basis for many of our studies with biophysical, molecular, and transgenic approaches. An important endpoint and success of our approaches has been the development of new drugs for use in the treatment of heart failure.
222. Kobayashi T, Yang X, Walker LA, Van Breemen RB, Solaro RJ. (2005) A non-equilibrium isoelectric focusing method to determine states of phosphorylation of cardiac troponin I : Identification of Ser-23 and Ser-24 as significant sites of phosphorylation by protein kinase C. J Mol Cell Cardiol 38:213-8. PMID: 15623438
223. Solaro RJ, Westfall MV. (2005) Physiology of the Myocardium. In: Surgery of the Chest (Sellke FW, del Nido PJ, Swanson SJ eds) Elsevier Sanders (Philadelphia, PA) pp 767-779.
224. Parmacek MS, Solaro RJ. (2005) Biology of the troponin complex in cardiac myocytes. Prog Card Dis 47:159-176. PMID: 15736582
225. Kobayashi T, Solaro RJ. (2005) Calcium, Thin Filaments, and Integrative Biology of Cardiac Contractility. Annu Rev Physiol 67:39-67. PMID: 15736582
226. Layland J, Solaro RJ, Shah AM. (2005) Regulation of cardiac contractile function by troponin I phosphorylation. Cardiovasc Res 66:12-21. PMID: 15769444
227. Layland J, Cave AC, Grieve DJ, Sparks E, Kentish JC, Warren C, Solaro RJ, Shah AM. (2005) Protection against endotoxaemia induced contractile dysfunction in mice with cardiac-specific expression of slow skeletal troponin I. FASEB J 19:1137-1139. PMID: 15961720
228. Vahebi S, Kobayashi T, Warren CM, de Tombe PP, R. Solaro RJ. (2005) Functional effects of Rho-kinase (ROCK-II) dependent phosphorylation of specific sites on cardiac troponin. Circ Res 96:740-747. PMID: 15855227
229. Urboniene D, Dias F, Peña JR, Walker LA, Solaro RJ, Wolska BM. (2005) Expression of slow skeletal troponin I in adult mouse heart helps to maintain the left ventricular systolic function during respiratory hypercapnia. Circ Res 97:70-77. PMID: 15961720
230. Solaro RJ, Hasenfuss G. (2005) Control of cardiac function in health and disease by mechanisms at the level of the sarcomere. In : Molecular Mechanism of Cardiac Hypertrophy and Failure (Walsh RA, ed) Taylor and Francis Group (London) pp 265-279
231. Arteaga GM, , Warren CM, Milutinovic S, Martin AF, Solaro RJ. (2005) Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia/reperfusion dysfunction. Am J Physiol Heart Circ Physiol 289:H2183-92 PMID: 16024565
232. Vahebi S, Solaro RJ. (2005) Cardiac sarcomeric function, small G-protein signaling, and heart failure. Panminerva Medica 47:133-42. PMID: 16462722
233. Solaro RJ. (2005) Remote control of A-band cardiac thin filament by the I-Z-I network of cardiac sarcomeres. Trends in Cardiovasc Med 15:148-152. PMID: 16099379
234. Kass D, Solaro RJ. (2006) Mechanisms and Use of Calcium Sensitizing Agents. Circulation 113:305-315. PMID: 16418450
235. Scruggs SB, Walker LA, Lyu T, Geenen DL, Solaro RJ, Buttrick PM, Goldspink PH. (2006) Partial Replacement of Cardiac Troponin I with a Non-Phosphorylatable Mutant at Serines 43/45 Attenuates the Contractile Dysfunction Associated with PKC epsilon Phosphorylation. J Mol Cell Cardiol 40:465-73
236. Kobayashi T, Solaro RJ. (2006) Increased Ca 2+ -affinity of cardiac thin filaments reconstituted with cardiomyopathy related mutant troponin I. J Biol Chem 281:13471-7.
237. Biesiadecki BJ, Solaro RJ. (2006) Invited Editorial. When hearts fail so does skeletal muscle: breaking a vicious cycle. Circ Res 98:1456-1458 PMID: 16794192
238. McCall SJ, Nassar R, Malouf NN, Saunders AJ, Oakeley AE, Henderson PM, Solaro RJ, Pielak GJ, Alexander KA, Anderson PAW. (2006) Development and contractility: cardiac troponin T isoforms and cytosolic calcium. Pediatric Res 60:276-281. PMID: 16857772
239. Pyle WG, de Tombe PP, Sumandea MP, Solaro RJ. (2006) Control of cardiac myofilaemt activation and PKC-ß II signaling through the actin capping protein, CapZ. J Mol Cell Cardiol 41:537-543. PMID: 16870209
240. Belin RJ, Sumandea MP, Kobayashi T, Walker LA, Rundell VL, Yukahakova M, Ruch SH, Geenen DL, Solaro RJ, de Tombe PP. (2006) Molecular mechanism of depressed left ventricular myofilament function in experimental left ventricular hypertrophy and congestive heart failure. Am J Physiol Heart Circ Physiol 291:H2344-53. PMID: 16815982
241. Solaro RJ, Arteaga GM. (2007) Heart failure, ischemia/reperfusion injury and cardiac troponin. In: Regulatory mechanisms of Striated Muscle Contraction (Ebashi S, Ohtsuki I, eds.) Adv Exp Med Biology 592:191-200. Springer (Tokyo) PMID: 17278366
242. Bupha-Intr T, Wattanapermpool J, Pena JR, Wolska BM, Solaro RJ. (2007) Myofilament response to Ca 2+ and Na + /H + exchanger activity in sex hormone elated protection of cardiac myocytes from deactivation in hypercapnic acidosis. Am J Physiol (Reg Integ) 292:R837-R843. PMID: 17038443
243. Engel PL , Kobayashi T, Biesiadecki B, Davis J, Tikunova S, Wu S, Solaro RJ. (2007) Identification of a region of troponin I important in signaling cross-bridge dependent activation of cardiac myofilaments. J Biol Chem. 282:183-93. Epub 2006 Nov 12. PMID : 17099250
244. Vahebi S, Ota A, Li M, Warren CM, de Tombe PP, Want Y, Solaro RJ. (2007) p38-MAPK Induced Dephosphorylation of Alpha-Tropomyosin is Associated with Depression of Myocardial Sarcomeric Tension and ATPase Activity. Circ Res 100 : 408-15. PMID : 17234967
245. Solaro RJ. (2007) Nitroxyl (HNO) Effects on Myocardium Provides New Insights into the Significance of Altered Myofilament Response to Calcium in Regulation of Contractility. J Physiol. 580: 697. PMID: 17347260
246. Hinken A, Solaro RJ. (2007) A Dominant Role of Intrinsic Regulation of Cardiac Molecular Motors in the Control of Ventricular Ejection and Relaxation. Physiology 22:73-80. PMID: 17420299
247. Davis JP, Alionte C, Kobayashi T, Solaro RJ, Swartz DR, Tikunova SB. (2007) Effects of thin and thick filament proteins on calcium binding and exchange with cardiac troponin C. Biophysical J 92 : 3195-206. PMID : 17293397
248. Ke Y, Lum H, Solaro, RJ. (2007) Dephosphorylation of Myosin regulatory Light Chain and Inhibition of Barrier Dysfunction Induced by P 21 Activated Kinase-1 in Endothelial Cells. Canadian J Physiol and Pharm. 85:28128. PMID: 17612635
249. Ke Y, Lei M, Collins TP, Rakovic S, Mattick PAD, Yamasaki M, Brodie MS, Terrar DA, Solaro RJ. (2007) Regulation of L-type calcium channel and delayed rectifier potassium channel activity by P 21 activated kinase-1 in guinea-pig sino-atrial node pacemaker cells. Circ Res. 100:1317-27 PMID: 17413045
250. Jagatheesan G, Rajan S, Petrashevskaya N, Schwartz A, Boivin G, Arteaga GM, Solaro RJ, Liggett SB, Wieczorek DF. (2007) Rescue of tropomyosin-induced familial hypertrophic cardiomyopathy mice by transgenesis. Am J Physiol Heart Circ Physiol.(In Press). PMID: 17416600.
251. Biesiadecki BJ, Kobayashi T, Walker JS, Solaro RJ , de Tombe PP. (2007) Troponin C G159D Mutation Blunts Myofilament Desensitization induced by Troponin I PKA Phosphorylation. Circ Res 100:1486-93. Apr 19; [Epub ahead of print] PMID: 17446435
252. Xiao L, Zhao Q, Du Y, Chao Y, Solaro RJ, Buttrick PM. (2007) PKC e increases phosphorylation of the cardiac myosin binding protein C at Serine 302 both in vitro and in vivo. Biochemistry, May 16; [Epub ahead of print] PMID: 17503784.
253. Rajan S, Ahmed RPH, Jagatheesan G, Petrashevskaya N, Boivin GP, Urboniene D, Arteaga GM, Wolska BM, Solaro RJ, Liggett SB, Wieczorek DF. (2007) Dilated cardiomyopathy mutant tropomyosin mice develop cardiac dysfunction with significantly deceased fractional shortening and myofilaments calcium sensitivity. Circ Res June 7 [Epub ahead of print]
254. Belin RJ, Sumandea MP, Allen EA, Schoenfelt K, Wang H, Solaro RJ, de Tombe PP. (2007)Augmented protein kinase C-alpha induced myofilament protein phosphorylation contributes to myofilaments dysfunction in experimental congestive heart failure. Circ Res June [Epub ahead of print]. PMID: 17556659
255. Solaro RJ. (2007)Translational medicine with a capital T, troponin T, that is. Circ Res. 2007; 101:114-115. PMID: 17641232
256. Sheehan KA, Ke Y, Solaro RJ. (2007) P 21 Activated kinase-1 and its role in integrated regulation of cardiac contractility. Am J Physiol. (In Press). PMID: 17609315
257. Solaro RJ. (2007) Mechanisms of the Frank-Starling law of the heart: the beat goes on. Biophys J (In Press).
258. Lei M, Ke Y, Solaro RJ.(2007) Pak1: steps towards understanding the regulatory mechanisms of pacemaker function of the heart. Future Medicine (Invited Editorial). (In Press)
259. Howarth JW, Meller J, Solaro RJ, Trewhella J, Rosevear PR. (2007) Phosphorylation-dependent conformational transition of the cardiac specific n-extension of troponin I in cardiac troponin. J Mol Biol. (In Press).
260. Wu SC, Solaro RJ (2007) Protein kinase C zeta: A novel regulator of both phosphorylation and de-phosphorylation of cardiac sarcomeric proteins. J Biol Chem (In Press).
Last updated: 08/27/07