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

subunits, Kir6.1 and Kii-6.2, and 3 sulphonylurea subunits, SURI, SUR2A and SUR2B
have been identified and found to form channels with specific charactenstics and tissue
sites. K. yi-1, channels are present at high density (several thousand channels per cell) in the
sarcolemmal and mitochondrial membranes of myocardial cells. It has been suggested
that SURI and Kir6.2 are found in pancreatic islets, SUR2A and Kir6.2 in cardiac and
skeletal muscle, and SUR213 and Kir6.1 in vascular smooth muscle. Unfortunately, the
mito K..
x., -p channel has not been cloned as yet.
Noma [23 11 originally hypothesized that opening of the surface or sarc K. %-I-p channel
produced by hypoxia, ischernia, or pharmacological Kxi-P openers would enhance the
shortening of the cardiac action potential duration (APD) by accelerating phase 3
repolarization. This enhanced phase 3 repolarization would inhibit calcium entry into the
cell via L-type channels and prevent calcium overload.
In addition, membrane hyperpolarization or the slowing of depolarization would also
inhibit calcium entry and slow or prevent the reversal of the sodium-calcium exchanger
that normally extrudes calcium in exchange for sodium. The result of these actions would
be a reduction in calcium overload during ischaemia and possibly early reperfusion and
subsequent
increased cell viability. Indeed, a number of early studies seemed to support
this theory.
Inoue et al [ 14 11 first identified an ATP-sensitive K channel in the inner mitochondrial
membrane (mito KA-I-p) in rat liver by patch clamping giant mitoplasts prepared from rat
liver mitochondria. These authors found that the mito KATP channel had several
characteristics similar to those of the sarc: KATP in that the channel was reversibly
inactivated by ATP applied to the matnx side and inhibited by glibenclamide.
23