This Article Full Text Full Text (PDF) All Versions of this Article: 97/1/70    most recent 01.RES.0000173849.68636.1ev1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Urboniene, D. Articles by Wolska, B. M. Search for Related Content PubMed PubMed Citation Articles by Urboniene, D. Articles by Wolska, B. M. Related Collections Contractile function Genetically altered mice

(Circulation Research. 2005;97:70.)
© 2005 American Heart Association, Inc.

Integrative Physiology

Expression of Slow Skeletal Troponin I in Adult Mouse Heart Helps to Maintain the Left Ventricular Systolic Function During Respiratory Hypercapnia

Dalia Urboniene, Fernando A.L. Dias, James R. Peña, Lori A. Walker, R. John Solaro, Beata M. Wolska

From the Center for Cardiovascular Research, Department of Physiology and Biophysics (D.U., L.A.W., R.J.S., B.M.W.) and Department of Medicine (F.A.L.D., J.R.P., L.A.W., B.M.W.), Section of Cardiology, University of Illinois at Chicago.

Correspondence to Dr Beata M. Wolska, University of Illinois at Chicago, Dept of Medicine, Section of Cardiology, 840 S Wood St (M/C 715), Chicago, IL 60612. E-mail bwolska{at}uic.edu

Compared with the adult, neonatal heart muscle is less sensitive to deactivation by acidic pH. We hypothesized that expression of slow skeletal troponin I (ssTnI), the embryonic isoform, in adult heart would help maintain left ventricular (LV) systolic function during respiratory hypercapnia. We assessed LV function by transthoracic 2D-targeted M-mode and pulsed Doppler echocardiography in transgenic (TG) mice in which cardiac TnI was replaced with ssTnI and in nontransgenic (NTG) littermates. Anesthetized mice were ventilated with either 100% oxygen or 35% CO₂ balanced with oxygen. Arterial blood pH with 35% CO₂ decreased to the same levels in both groups of animals. In the absence of propranolol, the LV fractional shortening was higher in TG compared with NTG mice throughout most of the experimental protocol. LV diastolic function was impaired in TG compared with NTG mice both at 100% oxygen and 35% CO₂ because E-to-A wave ratio of mitral flow was significantly lower, and E-wave deceleration time and LV isovolumic relaxation time were longer in TG compared with NTG mice. When compensatory mechanisms that occur through stimulation of ß-adrenergic receptors during hypercapnia were blocked by continuous perfusion with propranolol, we found that NTG mice died within 3 to 4 minutes after switching to 35% CO₂, whereas TG mice survived. Our experiments demonstrate the first evidence that specific replacement of cardiac TnI with ssTnI has a protective effect on the LV systolic function during hypercapnic acidosis in situ.

Key Words: troponin I • hypercapnia • acidosis

This article has been cited by other articles:

				N. J. Palpant, L. G. D'Alecy, and J. M. Metzger Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo FASEB J, May 1, 2009; 23(5): 1529 - 1540. [Abstract] [Full Text] [PDF]

				N. J. Palpant, S. M. Day, T. J. Herron, K. L. Converso, and J. M. Metzger Single histidine-substituted cardiac troponin I confers protection from age-related systolic and diastolic dysfunction Cardiovasc Res, November 1, 2008; 80(2): 209 - 218. [Abstract] [Full Text] [PDF]

				C. Yuan, Q. Sheng, H. Tang, Y. Li, R. Zeng, and R. J. Solaro Quantitative comparison of sarcomeric phosphoproteomes of neonatal and adult rat hearts Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H647 - H656. [Abstract] [Full Text] [PDF]

				Q.-Q. Huang, H. Z. Feng, J. Liu, J. Du, L. B. Stull, C. S. Moravec, X. Huang, and J.-P. Jin Co-expression of skeletal and cardiac troponin T decreases mouse cardiac function Am J Physiol Cell Physiol, January 1, 2008; 294(1): C213 - C222. [Abstract] [Full Text] [PDF]

				J. Liu, J. Du, C. Zhang, J. W. Walker, and X. Huang Progressive troponin I loss impairs cardiac relaxation and causes heart failure in mice Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1273 - H1281. [Abstract] [Full Text] [PDF]

				T. Bupha-Intr, J. Wattanapermpool, J. R. Pena, B. M. Wolska, and R. J. Solaro Myofilament response to Ca2+ and Na+/H+ exchanger activity in sex hormone-related protection of cardiac myocytes from deactivation in hypercapnic acidosis Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R837 - R843. [Abstract] [Full Text] [PDF]

				P. L. Engel, T. Kobayashi, B. Biesiadecki, J. Davis, S. Tikunova, S. Wu, and R. J. Solaro Identification of a Region of Troponin I Important in Signaling Cross-bridge-dependent Activation of Cardiac Myofilaments J. Biol. Chem., January 5, 2007; 282(1): 183 - 193. [Abstract] [Full Text] [PDF]

				O. Cazorla, S. Szilagyi, N. Vignier, G. Salazar, E. Kramer, G. Vassort, L. Carrier, and A. Lacampagne Length and protein kinase A modulations of myocytes in cardiac myosin binding protein C-deficient mice Cardiovasc Res, February 1, 2006; 69(2): 370 - 380. [Abstract] [Full Text] [PDF]

				D. A. Kass and R. J. Solaro Mechanisms and Use of Calcium-Sensitizing Agents in the Failing Heart Circulation, January 17, 2006; 113(2): 305 - 315. [Full Text] [PDF]