| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
UCLA Cardiovascular Research Laboratory, Department of Medicine.
1. The contribution of ATP-sensitive K+ (K+ATP) channels to the rapid increase in cellular K+ efflux and shortening of action potential duration (APD) during early myocardial ischaemia and hypoxia remains controversial, because for the first 10 min of ischaemia or hypoxia in intact hearts cytosolic [ATP] remains about two orders of magnitude greater than the [ATP] causing half-maximal blockade of K+ATP channels in excised membrane patches. The purpose of this study was to investigate this apparent discrepancy. 2. During substrate-free hypoxia, total, diastolic and systolic unidirectional K+ efflux rates increased by 43, 26 and 103% respectively after 8.3 min in isolated arterially perfused rabbit interventricular septa loaded with 42K+. APD shortened by 39%. From the Goldman-Hodgkin-Katz equation, the relative increases in systolic and diastolic K+ efflux rates were consistent with activation of a voltage-independent K+ conductance. 3. During total global ischaemia, [K+]o measured with intramyocardial valinomycin K(+)-sensitive electrodes increased at a maximal rate of 0.68 mM min-1, which could be explained by a less than 26% increase in unidirectional K+ efflux rate (assuming no change in K+ influx), less than the increase during hypoxia. APD shortened by 23% over 10 min. 4. During hypoxia and ischaemia, cytosolic [ATP] decreased by about one-third from 6.8 +/- 0.5 to 4.3 +/- 0.3 and 4.6 +/- 0.4 mM respectively, and free cytosolic [ADP] increased from 15 to 95 and approximately 63 microM respectively. 5. To estimate the percentage of activation of current through K+ATP channels (IK,ATP) necessary to double the systolic K+ efflux rate (comparable to the increase during hypoxia), K+ efflux during a single simulated action potential was measured by blocking non-K+ currents under control conditions and after IK,ATP was fully activated by metabolic inhibitors. Activation of 0.41 +/- 0.07% of maximal IK,ATP was sufficient to double the systolic K+ efflux rate. The equivalent amount of constant hyperpolarizing current also shortened the APD in the isolated myocytes by 41 +/- 5%, compared to the 39% APD shortening observed during hypoxia in the intact heart. 6. The degree of activation of IK,ATP expected to occur during hypoxia and ischaemia was estimated by characterizing the ATP sensitivity of K+ATP channels in the presence of 2 mM-free Mgi2+ and 0, 10, 100 and 300 microM-ADPi in inside-out membrane patches excised from guinea-pig ventricular myocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
This article has been cited by other articles:
|
|
 |
|
  L. V. Zingman, A. E. Alekseev, D. M. Hodgson-Zingman, and A. Terzic ATP-sensitive potassium channels: metabolic sensing and cardioprotection J Appl Physiol, November 1, 2007; 103(5): 1888 - 1893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Tice, B. Rodriguez, J. Eason, and N. Trayanova Mechanistic investigation into the arrhythmogenic role of transmural heterogeneities in regional ischaemia phase 1A Europace, November 1, 2007; 9(suppl_6): vi46 - vi58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-H. T. Nguyen, S. J. Dudycha, and M. S. Jafri Effect of Ca2+ on cardiac mitochondrial energy production is modulated by Na+ and H+ dynamics Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2004 - C2020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Selivanov, S. Krause, J. Roca, and M. Cascante Modeling of Spatial Metabolite Distributions in the Cardiac Sarcomere Biophys. J., May 15, 2007; 92(10): 3492 - 3500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Michailova, J. Saucerman, M. E. Belik, and A. D. McCulloch Modeling Regulation of Cardiac KATP and L-type Ca2+ Currents by ATP, ADP, and Mg2+ Biophys. J., March 1, 2005; 88(3): 2234 - 2249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Rodriguez, B. M. Tice, J. C. Eason, F. Aguel, J. M. Ferrero Jr., and N. Trayanova Effect of acute global ischemia on the upper limit of vulnerability: a simulation study Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2078 - H2088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. P. Flagg, F. Charpentier, J. Manning-Fox, M. S. Remedi, D. Enkvetchakul, A. Lopatin, J. Koster, and C. Nichols Remodeling of excitation-contraction coupling in transgenic mice expressing ATP-insensitive sarcolemmal KATP channels Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1361 - H1369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rodriguez, J. M. Ferrero Jr., and B. Trenor Mechanistic investigation of extracellular K+ accumulation during acute myocardial ischemia: a simulation study Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H490 - H500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Abraham, V. A. Selivanov, D. M. Hodgson, D. Pucar, L. V. Zingman, B. Wieringa, P. P. Dzeja, A. E. Alekseev, and A. Terzic Coupling of Cell Energetics with Membrane Metabolic Sensing. INTEGRATIVE SIGNALING THROUGH CREATINE KINASE PHOSPHOTRANSFER DISRUPTED BY M-CK GENE KNOCK-OUT J. Biol. Chem., June 28, 2002; 277(27): 24427 - 24434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, H. Wang, H. Han, Y. Zhang, B. Yang, S. Nattel, and Z. Wang Phospholipid Metabolite 1-Palmitoyl-Lysophosphatidylcholine Enhances Human Ether-a-Go-Go-Related Gene (HERG) K+ Channel Function Circulation, November 27, 2001; 104(22): 2645 - 2648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Nerbonne, C. G. Nichols, T. L. Schwarz, and D. Escande Genetic Manipulation of Cardiac K+ Channel Function in Mice: What Have We Learned, and Where Do We Go From Here? Circ. Res., November 23, 2001; 89(11): 944 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Knopp, S. Thierfelder, B. Doepner, and K. Benndorf Mitochondria are the main ATP source for a cytosolic pool controlling the activity of ATP-sensitive K+ channels in mouse cardiac myocytes Cardiovasc Res, November 1, 2001; 52(2): 236 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. M. Sejersted and G. Sjogaard Dynamics and Consequences of Potassium Shifts in Skeletal Muscle and Heart During Exercise Physiol Rev, October 1, 2000; 80(4): 1411 - 1481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M Mohan and D. J Paterson Activation of sulphonylurea-sensitive channels and the NO-cGMP pathway decreases the heart rate response to sympathetic nerve stimulation Cardiovasc Res, July 1, 2000; 47(1): 81 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Shaw and Y. Rudy Electrophysiologic effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration Cardiovasc Res, August 1, 1997; 35(2): 256 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Shaw and Y. Rudy Electrophysiologic Effects of Acute Myocardial Ischemia: A Mechanistic Investigation of Action Potential Conduction and Conduction Failure Circ. Res., January 1, 1997; 80(1): 124 - 138. [Abstract] [Full Text]
|
|
|
|
|
|
J. M. Ferrero, J. Saiz, J. M. Ferrero, and N. V. Thakor Simulation of Action Potentials From Metabolically Impaired Cardiac Myocytes: Role of ATP-Sensitive K+ Current Circ. Res., August 1, 1996; 79(2): 208 - 221. [Abstract] [Full Text]
|
|
|
|
|
|
J. C. Koster, A. Knopp, T. P. Flagg, K. P. Markova, Q. Sha, D. Enkvetchakul, T. Betsuyaku, K. A. Yamada, and C. G. Nichols Tolerance for ATP-Insensitive KATP Channels in Transgenic Mice Circ. Res., November 23, 2001; 89(11): 1022 - 1029. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
