| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received March 19, 2003
Accepted after revision May 6, 2003
1 Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
2 Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada
3 Department of Pharmacology, University of Alberta, 9-58 Medical Sciences, Edmonton, Alberta, Canada T6G 2H7
* To whom correspondence should be addressed. E-mail: peter.light{at}ualberta.ca.
In the heart, reperfusion following an ischaemic episode can result in a marked increase in [Ca2+]i and cause myocyte dysfunction and death. Although the Na+-Ca2+ exchanger has been implicated in this response, the ionic mechanisms that are responsible have not been identified. In this study, the hypothesis that the diastolic membrane potential can influence Na+-Ca2+ exchange and Ca2+ homeostasis during chemically induced hypoxia-reoxygenation has been tested using right ventricular myocytes isolated from adult rat hearts. Superfusion with selected [K+]o of 2.5, 5, 7, 10, 15 and 0.5 mM yielded the following resting membrane potentials: -102.2 ± 1.89, -86.5 ± 1.03, -80.1 ± 1.25, -73.6 ± 1.02, -66.4 ± 1.03 and -27.6 ± 1.63 mV, respectively. In a second set of experiments myocytes were subjected to chemically induced hypoxia-reoxygenation at these different [K+]o, while [Ca2+]i was monitored using fura-2. These results demonstrated that after chemically induced hypoxia-reoxygenation had caused a marked increase in [Ca2+]i, hyperpolarization of myocytes with 2.5 mM [K+]o significantly reduced [Ca2+]i (7.5 ± 0.32 vs. 16.9 ± 0.55 %); while depolarization (with either 0.5 or 15 mM [K+]o) significantly increased [Ca2+]i (31.8 ± 3.21 and 20.8 ± 0.36 vs. 16.9 ± 0.55 %, respectively). As expected, at depolarized membrane potentials myocyte hypercontracture and death increased in parallel with Ca2+ overload. The involvement of the Na+-Ca2+ exchanger in Ca2+ homeostasis was evaluated using the Na+-Ca2+ exchanger inhibitor KB-R7943. During reoxygenation KB-R7943 (5 µM) almost completely prevented the increase in [Ca2+]i both in control conditions (in 5 mM [K+]o: 2.2 ± 0.40 vs. 10.8 ± 0.14 %) and in depolarized myocytes (in 15 mM [K+]o: -2.1 ± 0.51 vs. 11.3 ± 0.05 %). These findings demonstrate that the resting membrane potential of ventricular myocytes is a critical determinant of [Ca2+]i during hypoxia-reoxygenation. This appears to be due mainly to an effect of diastolic membrane potential on the Na+-Ca2+ exchanger, since at depolarized potentials this exchanger mechanism operates in the reverse mode, causing a significant Ca2+ influx.
This article has been cited by other articles:
|
|
 |
|
  G. C. Rodrigo and N. J. Samani Ischemic preconditioning of the whole heart confers protection on subsequently isolated ventricular myocytes Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H524 - H531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Imahashi, F. Mraiche, C. Steenbergen, E. Murphy, and L. Fliegel Overexpression of the Na+/H+ exchanger and ischemia-reperfusion injury in the myocardium Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2237 - H2247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Chilton, S. Ohya, D. Freed, E. George, V. Drobic, Y. Shibukawa, K. A. MacCannell, Y. Imaizumi, R. B. Clark, I. M. C. Dixon, et al. K+ currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2931 - H2939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Akabas Na+/Ca2+ Exchange Inhibitors: Potential Drugs to Mitigate the Severity of Ischemic Injury Mol. Pharmacol., July 1, 2004; 66(1): 8 - 10. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bouchard, R. B. Clark, A. E. Juhasz, and W. R. Giles Changes in extracellular K+ concentration modulate contractility of rat and rabbit cardiac myocytes via the inward rectifier K+ current IK1 J. Physiol., May 1, 2004; 556(3): 773 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Eigel, H. Gursahani, and R. W. Hadley ROS are required for rapid reactivation of Na+/Ca2+ exchanger in hypoxic reoxygenated guinea pig ventricular myocytes Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H955 - H963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Gong, D. Legault, T. Miki, S. Seino, and J. M. Renaud KATP channels depress force by reducing action potential amplitude in mouse EDL and soleus muscle Am J Physiol Cell Physiol, December 1, 2003; 285(6): C1464 - C1474. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
