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Endothelium as target for large-conductance calcium-activated potassium channel openers

100%

Wrzosek A.

Acta Biochimica Polonica

2009

tom 56

nr 3

393-404

The endothelium is a highly active organ responsible for vasculatory tone and structure, angiogenesis, as well as hemodynamic, humoral, and inflammatory responses. The endothelium is constantly exposed to blood flow, sheer stress and tension. Endothelial cells are present as a vasculature in every tissue of the body and react to and control its microenvironment. A variety of ion channels are present in the plasma membranes of endothelial cells. These include potassium channels such as inwardly rectifying potassium (Kir) channels, voltage-dependent (Kv) channels, ATP-regulated potassium (KATP) channels and three types of calcium-activated potassium channels (KCa), the large (BKCa), intermediate (IKCa), and small (SKCa) -conductance potassium channels. Potassium current plays a critical role in action potentials in excitable cells, in setting the resting membrane potential, and in regulating neurotransmitter release. Mitochondrial isoforms of potassium channel contribute to the cytoprotection of endothelial cells. Prominent among potassium channels are families of calcium-activated potassium channels, and especially large-conductance calcium-activated potassium channels. The modulation of BKCa channels, which are voltage- and calcium-dependent, has been intensively studied. The BKCa channels show large expression dynamics in endothelial cells and tissue-specific expression of large numbers of alternatively spliced isoforms. In this review, a few examples of the modulatory mechanisms and physiological consequences of the expression of BKCa channels are discussed in relation to potential targets for pharmacological intervention.

Molecular dynamics simulations of potassium channels

75%

Domene C.

Open Chemistry

2007

tom 5

nr 3

635-671

Despite the complexity of ion-channels, MD simulations based on realistic all-atom models have become a powerful technique for providing accurate descriptions of the structure and dynamics of these systems, complementing and reinforcing experimental work. Successful multidisciplinary collaborations, progress in the experimental determination of three-dimensional structures of membrane proteins together with new algorithms for molecular simulations and the increasing speed and availability of supercomputers, have made possible a considerable progress in this area of biophysics. This review aims at highlighting some of the work in the area of potassium channels and molecular dynamics simulations where numerous fundamental questions about the structure, function, folding and dynamics of these systems remain as yet unresolved challenges. [...]