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New modes of exchanger regulation: physiological implications
John P Reeves1, Madalina Condrescu, Jason Urbanczyk
1Department of Pharmacology & Physiology, UMDNJ-Graduate School of Biomedical Sciences, 185 South Orange Avenue, P.O. Box 1709, Newark, NJ 07103, USA. reeves@umdnj.edu
Annals of the New York Academy of Sciences
|April 21, 2007
Summary
Cytosolic sodium (Na+) and calcium (Ca2+) regulate exchange activity in cardiac cells. New findings suggest that Ca2+ transients over multiple heartbeats, not beat-to-beat, may control this activity.
Area of Science:
- Cardiovascular Physiology
- Cellular Signaling
- Ion Transport
Background:
- Cytosolic sodium (Na+), calcium (Ca2+), and phosphatidylinositol 4,5-bisphosphate (PIP2) are key regulators of exchange activity.
- Previous studies using excised patches suggest these regulatory mechanisms are not ideal for beat-to-beat control of exchange activity.
Purpose of the Study:
- To investigate novel regulatory mechanisms of exchange activity in cardiac myocytes.
- To determine if exchange activity regulation is suited for beat-to-beat control or longer-term integration of signals.
Main Methods:
- Analysis of allosteric Ca2+ activation and its hysteresis.
- Examination of Na+-induced activity independent of Ca2+.
- Assessment of PIP2 requirement after Ca2+ activation.
Main Results:
- Allosteric Ca2+ activation of exchange activity exhibits hysteresis.
- High cytosolic Na+ concentrations induce a Ca2+-independent mode of activity.
- The requirement for PIP2 is diminished or abolished following allosteric Ca2+ activation.
Conclusions:
- Exchange activity regulation in cardiac myocytes may involve integration of Ca2+ transients over multiple cardiac cycles.
- This suggests a mechanism for adapting exchange activity based on cumulative Ca2+ signaling history rather than instantaneous levels.
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