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| Phosphotransfer reactions in the regulation of ATP-sensitive K+ channels |
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| Author(s): Dzeja PP, Terzic A |
| Source: FASEB JOURNAL Volume: 12 Issue: 7 Pages: 523-529 Published: MAY 1998 |
| Times Cited: 75 References: 72 |
| Abstract: ATP-sensitive K+ (K-ATP) channels are nucleotide-gated channels that couple the metabolic status of a cell with membrane excitability and regulate a number of cellular functions, including hormone secretion and cardioprotection, Although intracellular ATP is the endogenous inhibitor of K-ATP channels and ADP serves as the channel activator, it is still a matter of debate whether changes in the intracellular concentrations of ATP, ADP, and/or in the ATP/ADP ratio could account for the transition from the ATP-liganded to the ADP-liganded channel state. Here, we overview evidence for the role of cellular phosphotransfer cascades in the regulation of K-ATP channels. The microenvironment of the K-ATP channel harbors several phosphotransfer enzymes, including adenylate, creatine, and pyruvate kinases, as well as other glycolytic enzymes that are able to transfer phosphoryls between ATP and ADP in the absence of major changes in cytosolic levels of adenine nucleotides, These phosphotransfer reactions are governed by the metabolic status of a cell, and their phosphotransfer rate closely correlates with K-ATP channel activity. Adenylate kinase catalysis accelerates the transition from ATP to ADP, leading to K-ATP channel opening, while phosphotransfers driven by creatine and pyruvate kinases promote ADP to ATP transition and channel closure. Thus, through delivery and removal of adenine nucleotides at the channel site, phosphotransfer reactions could regulate ATP/ADP balance in the immediate vicinity of the channel and thereby the probability of K-ATP channel opening. In this way, phosphotransfer reactions could provide a transduction mechanism coupling cellular metabolic signals with K-ATP channel-associated functions. |
| Document Type: Review |
| Language: English |
| Reprint Address: Terzic, A (reprint author), Mayo Clin & Mayo Fdn, Dept Med, Div Cardiovasc Dis, Guggenheim 7, Rochester, MN 55905 USA |
Addresses:
1. Mayo Clin & Mayo Fdn, Dept Med, Div Cardiovasc Dis, Rochester, MN 55905 USA
2. Mayo Clin & Mayo Fdn, Dept Pharmacol, Rochester, MN 55905 USA |
| Publisher: FEDERATION AMER SOC EXP BIOL, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA |
| Subject Category: Biochemistry & Molecular Biology; Biology; Cell Biology |
| IDS Number: ZM284 |
| ISSN: 0892-6638 |
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