NIH FIRCA R03 TW 00949

Coupled gating between intracellular calcium release channels

Principal Investigator: Andrew R. Marks, Columbia University, New York, NY, USA

International Collaborators: Karol Ondriaš, Marta Gaburjáková

Duration May 1998 – June 2006

Coordinating Organization: Columbia University, New York, NY, USA


The objective of the FIRCA project is to elucidate structure-function relationships of intracellular calcium release channels. In the last  years important advances have been achieved in terms of identifying functional domains of the channels and in understanding the role of (FKBP12/12.6 protein in regulating function of the ryanodine receptor (RYR) that functions as a intracellular Ca2+ channel. Significant new findings and preliminary data provided by prof. A.R. Marks include: 1) FKBP12/12.6 stabilizes the RyR function in both sekeltal and cardiac muscle; 2) identification of the binding site for FKBP12/12.6 on the RYR channel; 3) RyR channels are physically bound to neighboring RYR channels and 2 or more channels can exhibit “coupled gating” in planar lipid bilayers (believed to be important for controlling excitation-contraction coupling). The proposed collaboration between the laboratories of prof. A R. Marks (Columbia University, New York, NY, USA) and dr. K. Ondrias (Slovak Academy of Sciences, Bratislava, Slovakia) should mostly cover  the heterologous functional expression of ion channels and their reconstitution in artificial membrane systems.


Ca2+ channel, FKBP12/12.6, gen mutation, planar lipid membrane, muscle contraction, ryanodin, Sf9 cell line, T lymphocyte


1. Characterize coupled gating between cardiac ryanodine receptors

2. Determine whether inositol 1,4,5-trisphosphate receptors (IP3R) exhibit coupled gating

3. Determine the functional role of coupled gating between IP3R channels in T lymphocyte activation