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

activity, and showed that diazoxide induced oxidation at concentrations that correlated
well with its card
ioprotective effects, but which did not activate sarcolemmal K: %,,,
channels. The present study provides evidence for the first time that opening of mitoK,. %.,,,,
channels may be responsible for the protection induced by ischaemic preconditioning in
the human myocardium.
Kxrp channels are composed of 2 proteins, an inwardly rectifying potassium channel
(Kir 6. x) and a sulphonylurea receptor (SUR) subunit. It has been suggested that SUR2A
and Kir 6.2 are found in cardiac sarcolernma. Unfortunately, to date the mito Kxj 1,
channel has not been cloned as yet but there are suggestions that Kir 6.1 subunit 12931 is
involved in the milochondrial membrane of the rat skeletal muscle and
liver. Certainly,
mitochondrial and sarcolemmal KATP channels appear to exhibit minor differences in
structure but the function of the mitochondrial K.,
%-I-p channels appear to be intimately
involved in matrix volume control as opposed to electrical activity for sarcolemmal K.. %, -,,
channels. In this instance, opening of the mitoK.. %-Fp channel leads to membrane
depolarization, matrix swelling, slowing of ATP synthesis, and accelerated respiration
[1081. There is good evidence that diazoxide and 5-HD show good selectivity for
mitochondrial over cardiac sarcolernmal K.,
%, -,, channels [99,266] and this present study
confirms that preconditioning can be mimicked with diazoxide and abolished with both
5-HD and glibenclamide. These results are in close agreement with those of Garlid et al
[991 and further suggest that the mitoKATP channels are the possible effectors of
cardioprotection produced by ischaemic preconditioning. To more clearly address this
issue, I used a specific sarcolemmal KATP channel blocker, HMR 1883. The novel blocker
HMR 1883 shows good selectivity for the cardiac sarcolernmal K.. %-I-p channel over those
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