New modes of exchanger regulation: physiological implications.
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.
Reeves
John P
JP
Department of Pharmacology & Physiology, UMDNJ-Graduate School of Biomedical Sciences, 185 South Orange Avenue, P.O. Box 1709, Newark, NJ 07103, USA. reeves@umdnj.edu
Condrescu
Madalina
M
Urbanczyk
Jason
J
Chernysh
Olga
O
D000494:Allosteric Regulation; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000502:physiology*
D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium