HHMI-75195547801

Ryanodine receptor and excitation-contraction coupling

Principal Investigator: Alexandra Zahradníková

Duration: April 1995 – August 2000
Coordinating Organization: Institute of Molecular Physiology and Genetics SAS, Bratislava

Annotation:

The cardiac ryanodine receptor (RyR) is a membrane protein located in the junctional sarcoplasmic reticulum (jSR), where it functions as a calcium release channel. The jSR is in close apposition to the membrane of t-tubules containing the L-type calcium channel (DHPR), which triggers calcium release from the SR when the influx of Ca2+ ions through the DHPR following membrane depolarization activates nearby RyRs (calcium-induced calcium release, CICR). We propose that the global conformational changes of the RyR (gating modes) play an important role in the response of the RyR to both, brief and sustained stimuli.

Keywords:

ryanodine receptor, modal gating, mathematical models, planar lipid bilayers

Objectives:

The aim of the project is to elucidate the mechanism of modal transition of the RyR channel and to determine their impact on the gradation and termination of calcium-induced calcium release, using a combination of experimental and theoretical approaches.

Publications:

	Dura M, Zahradnik I, Zahradnikova A (2003): Kinetics of cardiac RyR channel gating studied at high temporal resolution. Physiol Res. 52: 571-578.
	Zahradnikova A, Dura M, Gyorke S (1999): Modal gating transitions in cardiac ryanodine receptors during increases of Ca2+ concentration produced by photolysis of caged Ca2+. Pflugers Arch. 438: 283-288.
	Zahradnikova A, Zahradnik I (1999): Analysis of calcium-induced calcium release in cardiac sarcoplasmic reticulum vesicles using models derived from single-channel data. Biochimica Et Biophys Acta-Biomembr. 1418: 268-284.
	Zahradnikova A, Zahradnik I, Gyorke I, Gyorke S (1999). Rapid activation of the cardiac ryanodine receptor by submillisecond calcium stimuli. J Gen Physiol. 114: 787-798.
	Meszaros L G, Zahradnikova A, Volpe P (1998): Kinetic basis of quantal calcium release from intracellular calcium stoves. Cell Calcium. 23: 43-52.
	Zahradnikova A, Meszaros L G (1998). Voltage change-induced gating transitions of the rabbit skeletal muscle Ca2+ release channel. J. Physiol. 509: 29-38.
	Zahradnikova A, Minarovic I, Venema R C, Meszaros L G (1997): Inactivation of the cardiac ryanodine receptor calcium release channel by nitric oxide. Cell Calcium. 22: 447-453.
	Zahradnikova A, Zahradnik I (1996). A minimal gating model for the cardiac calcium release channel. Biophys J. 71: 2996-3012.