The role of heme in ion channel function

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The involvement of the metallic element iron in various biological systems is well known. In many cases, iron is employed in the form of a heme group, most famously in hemoglobin. The family of heme proteins is vast, and the involvement of heme in these proteins is as a prosthetic group, in which the heme is tightly associated with the protein structure. Extensive studies have shown that the binding of heme to a particular protein defines the reactivity of that molecule. In this way a large number of biological requirements - such as oxygen transport, catalytic oxidation of all kinds of substrates, synthesis of NO, electron transfer etc - become accessible through incorporation of the same heme group into different protein structures. Very recently, it is becoming clear that the description above represents only a small part of a much more complex biological role for heme and that other, regulatory roles for heme have been overlooked. One example is in the regulation of ion channel function. Ion channel proteins form a pore through which ions (e.g. potassium, calcium, sodium) can travel through cell membranes. These channels have gates that open and close, and thus regulate the flow of ions through the pore. This ion flow governs many important biological processes such as beating of the heart and brain function. There is emerging evidence that heme can control opening and closing of these ion channel gates. Through a collaboration with the established cell physiology group at Leicester, and by incorporation of computational and proteomic approaches, we intend to build a more detailed description of how heme exerts these regulatory effects in a number of different ion channels.