GridPP: the UK grid for particle physics.

The start-up of the Large Hadron Collider (LHC) at CERN, Geneva, presents a huge challenge in processing and analysing the vast amounts of scientific data that will be produced. The architecture of the worldwide grid that will handle 15 PB of particle physics data annually from this machine is based on a hierarchical tiered structure. We describe the development of the UK component (GridPP) of this grid from a prototype system to a full exploitation grid for real data analysis. This includes the physical infrastructure, the deployment of middleware, operational experience and the initial exploitation by the major LHC experiments.

Immunogold-labeled L-type calcium channels are clustered in the surface plasma membrane overlying junctional sarcoplasmic reticulum in guinea-pig myocytes-implications for excitation-contraction coupling in cardiac muscle.

Ca(2+) release through ryanodine receptors, located in the membrane of the junctional sarcoplasmic reticulum (SR), initiates contraction of cardiac muscle. Ca(2+)influx through plasma membrane L-type Ca(2+)channels is thought to be an important trigger for opening ryanodine receptors ("Ca(2+)-induced Ca(2+)-release"). Optimal transmission of the transmembrane Ca(2+)influx signal to SR release is predicted to involve spatial juxtaposition of L-type Ca(2+)channels to the ryanodine receptors of the junctional SR. Although such spatial coupling has often been implicitly assumed, and data from immunofluorescence microscopy are consistent with its existence, the definitive demonstration of such a structural organization in mammalian tissue is lacking at the electron-microscopic level. To determine the spatial distribution of plasma membrane L-type Ca(2+)channels and their location in relation to underlying junctional SR, we applied two high-resolution immunogold-labeling techniques, label-fracture and cryothin-sectioning, combined with quantitative analysis, to guinea-pig ventricular myocytes. Label-fracture enabled visualization of colloidal gold-labeled L-type Ca(2+)channels in planar freeze-fracture electron-microscopic views of the plasma membrane. Mathematical analysis of the gold label distribution (by nearest-neighbor distance distribution and the radial distribution function) demonstrated genuine clustering of the labeled channels. Gold-labeled cryosections showed that labeled L-type Ca(2+)channels quantitatively predominated in domains of the plasma membrane overlying junctional SR. These findings provide an ultrastructural basis for functional coupling between L-type Ca(2+)channels and junctional SR and for excitation-contraction coupling in guinea-pig cardiac muscle.