Manganese and intracellular Ca2+ handling

The presence of significant amounts of the transition metal, manganese, is essential for living cells where it is bound to some intracellular enzymes. The free (i.e., unbound) Mn2+ concentration in both extracellular and intracellular space is tightly regulated and thought to be considerably lower than the free calcium ion (Ca2+) concentration. Mn2+ can pass through plasmalemma Ca2+ ion channels, but under normal circumstances due to channel selectivity and relative concentrations, this event is rare. But when extracellular Mn2+ is increased to mM levels, significant Mn2+ influx occurs through Ca2+ channels in the plasma membrane and intracellular manganese levels increase above normal physiological levels. Mn2+ ions also have the property of binding to and quenching the fluorescence of fluorophores. This property can be used to detect Mn2+ influx and is the basis of the use of raised extracellular Mn2+ in experiments designed to detect pathways for Ca2+ influx. This commentary features the manganese quench technique as used in a recently published article and discusses in detail the potential consequences for the intracellular Ca2+ handling when intracellular Mn2+ is increased, as it now competes to a greater extent than normal with Ca2+ for intracellular buffers.