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Physiological Implications
a Department of Pharmacology & Physiology, UMDNJ—Graduate School of Biomedical Sciences, Newark, New Jersey 07103, USA
Key Words: phosphatidylinositol-4,5-bisphosphate (PIP2) • hysteresis • allosteric calcium activation • fura-2
Address for correspondence: John P. Reeves, Department of Pharmacology & Physiology, UMDNJ—Graduate School of Biomedical Sciences, 185 South Orange Avenue, P.O. Box 1709, Newark, NJ 07103. Voice: 973-972-3890; fax: 973-972-7950. reeves{at}umdnj.edu
Exchange activity is regulated principally by cytosolic Na+, Ca2+, and PIP2. However, the properties of these modes of regulation that have emerged from excised patch studies appear to be poorly suited to regulating exchange activity on a beat-to-beat basis. Here we summarize recent findings from our lab indicating that (a) allosteric activation by Ca2+ exhibits hysteresis, (b) elevated concentrations of cytosolic Na+ induce a mode of activity that no longer requires regulatory Ca2+ activation, and (c) the requirement for PIP2 is reduced or eliminated after allosteric Ca2+ activation. Our results suggest that exchange activity in cardiac myocytes may be regulated by the time-integral of Ca2+ transients occurring over multiple beats.
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