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ischaemic preconditioning of the human heart. - Leicester Research ...

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and relationship <strong>of</strong> this channel to myocardial protection will be discussed in detail<br />

below<br />

[on channels are proteins that span cell membranes and make <strong>the</strong>m permeable to<br />

physiological ions, with channel proteins being selective to particular ions. An aqueous<br />

pore runs through <strong>the</strong> protein from inside to <strong>the</strong> outside <strong>of</strong> <strong>the</strong> membrane, through which<br />

ions can flow passively, down <strong>the</strong> electrochemical gradient. This mode <strong>of</strong> passive flow<br />

through <strong>the</strong> K+ channel is in common with that <strong>of</strong> o<strong>the</strong>r types <strong>of</strong> ion channel. Electrical<br />

current is carried when <strong>the</strong>re is a flow <strong>of</strong> ions through <strong>the</strong> channel, and high rate <strong>of</strong> ion<br />

allows currents to be measured even from a single channel, as well as from whole cells<br />

by <strong>the</strong> electrophysiological technique <strong>of</strong> patch clamping.<br />

The pore <strong>of</strong> most K+ channels can be opened or closed, that is to say <strong>the</strong>y are gated,<br />

by a conformational change in <strong>the</strong> protein molecule. Potassium channels are specific for<br />

K+, but differ by <strong>the</strong> factors which regulate gate opening or closing, or in <strong>the</strong> rate <strong>of</strong> K+<br />

flow through an open channel. Channels can be fur<strong>the</strong>r subdivided depending on whe<strong>the</strong>r<br />

gating is dependent primarily on membrane potential, voltage gated channels, or whe<strong>the</strong>r<br />

it is linked to binding <strong>of</strong> a specific chemical ligand, ligand-gated channelsI- although<br />

ligand-gated channels <strong>of</strong>ien show some voltage sensitivity as well. ATP-sensitive K+<br />

channels have a specific K+ selective pore, and intracellular ATP plays an important role<br />

in <strong>the</strong>ir gating. These channels provide a unique link between potassium permeability and<br />

action potential to cellular metabolism. K., %., -p channels are found in excitable tissues such<br />

as <strong>the</strong> <strong>heart</strong>, skeletal and smooth muscle, neurones and pancreatic P-cells, and link <strong>the</strong><br />

excitability <strong>of</strong> <strong>the</strong> cells to <strong>the</strong> metabolic state [9].<br />

19

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