New Modes of Exchanger Regulation Physiological Implications

摘要

Exchange activity is regulated principally by cytosolic Na~+, Ca~(2+), 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 Ca~(2+) exhibits hysteresis, (b) elevated concentrations of cytosolic Na~+ induce a mode of activity that no longer requires regulatory Ca~(2+) activation, and (c) the requirement for PIP2 is reduced or eliminated after allosteric Ca~(2+) activation. Our results suggest that exchange activity in cardiac myocytes may be regulated by the time-integral of Ca~(2+) transients occurring over multiple beats.