When LDH says "open," channels listen
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《细胞学杂志》
Jovanovic/Oxford
Achannel that protects cardiac cells from ischemia uses a rapid metabolite detection system to perceive dangerous conditions, according to new results from Russell Crawford, Aleksander Jovanovic, and colleagues (University of Dundee, Dundee, UK).
A heart attack damages cells when anaerobic conditions disrupt active ion transport, leading to a toxic increase in intracellular Ca2+. A decrease in ATP levels initially impairs ion transport, causing depolarization and Ca2+ import. However, low ATP may also trigger opening of ATP-sensitive K+ (K+ATP) channels, which would counteract the depolarization, ultimately reducing the time for Ca2+ influx.
But ATP regulation is not the whole story, as K+ATP channels open before intracellular ATP levels drop enough to open the channel. This prompted the group to search for additional components. They have now found that lactate dehydrogenase (LDH) interacts directly with the channel subunits. LDH catalyzes the reversible conversion of pyruvate to lactate, and thus may supply a local concentration of lactate to the channel. Indeed, the group demonstrated that lactate opened the channel despite high levels of ATP. Further, this regulated opening was crucial for the channel's ability to protect from ischemia.
Reference:
Crawford, R.M., et al. 2002. EMBO J. 21:3936–3948.(Ca2+ increase (white) in injured cells i)
Achannel that protects cardiac cells from ischemia uses a rapid metabolite detection system to perceive dangerous conditions, according to new results from Russell Crawford, Aleksander Jovanovic, and colleagues (University of Dundee, Dundee, UK).
A heart attack damages cells when anaerobic conditions disrupt active ion transport, leading to a toxic increase in intracellular Ca2+. A decrease in ATP levels initially impairs ion transport, causing depolarization and Ca2+ import. However, low ATP may also trigger opening of ATP-sensitive K+ (K+ATP) channels, which would counteract the depolarization, ultimately reducing the time for Ca2+ influx.
But ATP regulation is not the whole story, as K+ATP channels open before intracellular ATP levels drop enough to open the channel. This prompted the group to search for additional components. They have now found that lactate dehydrogenase (LDH) interacts directly with the channel subunits. LDH catalyzes the reversible conversion of pyruvate to lactate, and thus may supply a local concentration of lactate to the channel. Indeed, the group demonstrated that lactate opened the channel despite high levels of ATP. Further, this regulated opening was crucial for the channel's ability to protect from ischemia.
Reference:
Crawford, R.M., et al. 2002. EMBO J. 21:3936–3948.(Ca2+ increase (white) in injured cells i)