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

K vi-1, channels were initially found in cardiac muscle in 1983 by Noma [23 11, but
have since been identified in other tissues eg. skeletal and smooth muscle, pancreatic P-
cells, certain neurones and epithelial cells. It is interesting to note that the properties of
K..
\I, p channels differ between these tissues.
ATP probably binds to the sites on the protein to cause closure of the channel.
The ATP
binding site is known to be intracellular. Since ATP is ineffectual when outside the cell
[721, the Kxrp channel provides a mechanism for linking membrane potassium
permeability to cellular metabolism 12311. Intracellular factors affecting cardiac K.. %. I. p
channels include adenosine diphosphate (ADP), lactate and intracellular pH. It has been
shown that it is the ADP/ATP ratio, rather than the ATP alone, that may exert a more
sensitive control on the K..
%, -,, channel [79]. Intracellular pH changes rapidly during
hypoxia and ischaernia and this has been shown to affect these channels, with a fall in pH
causing a decrease
in the sensitivity to ATP, and so to channel inactivation by ATP [ 1741.
Intracellular lactate also activates cardiac K:
%. I. p channels [ 1661. These regulating factors
change more rapidly than ATP itself during ischaemia/hypoxia, and all cause a shift in
the ATP-inhibition curve, such that they reduce channel inhibition by ATP, ie. they cause
an increase in KATP channel open probability at a fixed ATP concentration [79,1741.
Activation of the K,
%. I-p channel is inhibited (closed) at physiological levels of intracellular
ATP and open when the intracellular ATP concentration falls.
In addition to regulation by metabolic factors acting within the cytosol, K:
ý. p channels
maybe modulated by transmitters that activate membrane receptors linked to G-proteins.
In ventricular myocytes, adenosine extracellularly binding to an adenosine receptor (A I)
appears to activate KATP channels by way of the alpha-subunit of the pertussis toxin
20