Regulation of Intracellular Calcium Release in Heart

Meissner, Gerhard

Abstract

This part of the Program Project deals with the sarcoplasmic reticulum and surface membrane of cardiac muscle. Its overall aim is to determine how these two membrane systems regulate the myoplasmic Ca2+ concentration in cardiac muscle and how this regulatory process is altered in ischemic muscle cells. In isolated sarcoplasmic reticulum membrane preparations, a """"""""Ca2+ release channel"""""""" mediates Ca2+ fluxes with physiological rates suggesting a role in excitation-contraction coupling in muscle. Regulation of this channel by Ca2+, Mg2+, adenine nucleotides, calmodulin, and other factors will be determined, using radioisotope flux - rapid quench techniques. In addition, Ca2+ release channels of cardiac sarcoplasmic reticulum will be incorporated into planar lipid bilayers so that single channel conductance, ion selectively and voltage-dependence, as well as the kinetics of channel opening and closing can be investigated. The effect of drugs will be tested to suggest ways of identifying and purifying the Ca2+ release channel components as well as modifying Ca2+ release in vivo. The Ca2+ permeability and Ca2+ transport properties of the surface membrane will be analyzed with membrane fractions isolated from ischemic and nonischemic hearts.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Heart, Lung, and Blood Institute (NHLBI)
• Type: Research Program Projects (P01)
• Project #: 5P01HL027430-13
• Application #: 3736281
• Support Year: 13
• Fiscal Year: 1995

Institution

• Name: University of North Carolina Chapel Hill
• DUNS #: 078861598
• City: Chapel Hill
• State: NC
• Country: United States
• Zip Code: 27599

Publications

Cole, R T; Lucas, C L; Cascio, W E et al. (2005) A LabVIEW model incorporating an open-loop arterial impedance and a closed-loop circulatory system. Ann Biomed Eng 33:1555-73

Cascio, Wayne E; Yang, Hua; Muller-Borer, Barbara J et al. (2005) Ischemia-induced arrhythmia: the role of connexins, gap junctions, and attendant changes in impulse propagation. J Electrocardiol 38:55-9

Xu, Le; Meissner, Gerhard (2004) Mechanism of calmodulin inhibition of cardiac sarcoplasmic reticulum Ca2+ release channel (ryanodine receptor). Biophys J 86:797-804

Kim, Chang-Soo; Ufer, Stefan; Seagle, Christopher M et al. (2004) Use of micromachined probes for the recording of cardiac electrograms in isolated heart tissues. Biosens Bioelectron 19:1109-16

Stange, Mirko; Xu, Le; Balshaw, David et al. (2003) Characterization of recombinant skeletal muscle (Ser-2843) and cardiac muscle (Ser-2809) ryanodine receptor phosphorylation mutants. J Biol Chem 278:51693-702

Bidasee, Keshore R; Xu, Le; Meissner, Gerhard et al. (2003) Diketopyridylryanodine has three concentration-dependent effects on the cardiac calcium-release channel/ryanodine receptor. J Biol Chem 278:14237-48

Sun, Junhui; Xu, Le; Eu, Jerry P et al. (2003) Nitric oxide, NOC-12, and S-nitrosoglutathione modulate the skeletal muscle calcium release channel/ryanodine receptor by different mechanisms. An allosteric function for O2 in S-nitrosylation of the channel. J Biol Chem 278:8184-9

Yamaguchi, Naohiro; Xu, Le; Pasek, Daniel A et al. (2003) Molecular basis of calmodulin binding to cardiac muscle Ca(2+) release channel (ryanodine receptor). J Biol Chem 278:23480-6

Graff, Ronald D; Kelley, Scott S; Lee, Greta M (2003) Role of pericellular matrix in development of a mechanically functional neocartilage. Biotechnol Bioeng 82:457-64

Lemasters, John J; Qian, Ting; He, Lihua et al. (2002) Role of mitochondrial inner membrane permeabilization in necrotic cell death, apoptosis, and autophagy. Antioxid Redox Signal 4:769-81