Imbalances in cytosolic calcium levels are often the central cause of both contractile dysfunction and heart arrhythmias that can lead to heart disease. The sodium/calcium exchanger (NCX) is the dominant calcium efflux mechanism in the heart that rapidly ejects large amounts of calcium from the cytosol after the muscle contraction phase.

In ischemia and multiple sclerosis NCX may play a damaging role as the ion transporter under pathological conditions rather imports than exports calcium.

In order to better understand the mechanism of sodium/calcium exchange, we plan to explore the structure of intact NCX by electron microscopy and/or X-ray crystallography.

An investigation of the two main states, the calcium free (inactive) and calcium bound (active) form, should provide a structural basis for the design of specific drugs that directed to control of calcium concentration in the cell or to prevent NCX from operating in reverse mode.