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

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sensitive G-protein (Gi, see Figure below) [ 1691. The G protein activation pathway may<br />

modulate <strong>the</strong> sensitivity <strong>of</strong> <strong>the</strong> Kxn, channel to inhibition by ATP, so acting via a similar<br />

manner to <strong>the</strong> metabolic regulators [143]. The activity <strong>of</strong> KATP channels can also be<br />

modulated by phosphorylation, which might come about by activation <strong>of</strong> protein kinase C<br />

(PKC) [9].<br />

O<strong>the</strong>r factors that influence <strong>the</strong> state <strong>of</strong> <strong>the</strong> K.<br />

\ý, -,, channel include <strong>the</strong> binding <strong>of</strong> Mg2+<br />

salts <strong>of</strong> nucleoside diphosphates (NDP) , such as Mg ADP and Mg GDP to an activating<br />

site on <strong>the</strong> channel. The activating site is different from <strong>the</strong> inhibitory ATP site.<br />

Therefore <strong>the</strong> opening <strong>of</strong> K. yI. 1, channels is regulated by <strong>the</strong> quotient <strong>of</strong> ATP/NDP [9].<br />

extracellular<br />

Noradrenalinc<br />

Gi<br />

oy<br />

GDP<br />

GTP<br />

The physiological role <strong>of</strong> <strong>the</strong> K. \.,,,, channels depends on <strong>the</strong> tissue. Those found<br />

in pancreatic P-cells determine <strong>the</strong> resting membrane potential and regulate insulin<br />

release in response to <strong>the</strong> plasma glucose levels. When glucose is taken up by <strong>the</strong><br />

pancreatic P-cells, this causes an increase in ATP concentration near <strong>the</strong> channel, so<br />

closing <strong>the</strong> K.,<br />

\.,.,, channel which depolarises <strong>the</strong> 0-cell and leads to Ca2+ entry into <strong>the</strong><br />

cell via voltage-gated calcium channels , so inducing insulin secretion [9]. In many<br />

21<br />

KATI'channel<br />

initochondrial

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