Delayed activation of the plasma membrane calcium pump by a sudden increase in Ca2+: fast pumps reside in fast cells

There are four genes encoding isoforms of the plasma membrane Ca2+ pump (PM CA). PMCA variability is increased by the presence of two splicing sites. F unctional differences between the variants of PMCA have been described, but little is known about the adaptive advantages of this great diversity of p umps. In this paper we studied how the different isoforms respond to a sudd en increase in Ca2+ concentration. We found that different PMCAs are activa ted by Ca2+ at different rates, PMCA 3f and 2a being the fastest, and 4b th e slowest. The rate of activation by Ca2+ depends both on the rate of calmo dulin binding and the magnitude of the activation by calmodulin. We found t hat 2a is located in heart and the stereocilia of inner ear hair cells, 3f in skeletal muscle and 4b was identified in Jurkat cells. Both cardiac and skeletal muscle, and stereocilia recover very rapidly after a cytoplasmic C a2+ peak, while in Jurkat cells the recovery takes up to a minute. In stere ocilia, 2a is the only method for export of Ca2+, making the analysis of th em unusually straightforward. This indicates that these rates of PMCA activ ation by Ca2+ are correlated with the speed of Ca2+ concentration decay aft er a Ca2+ spike in the cells in which these variants of PMCA are expressed. The results suggest that the type of PMCA expressed will correspond with t he speed of Ca2+ signals in the cell. (C) 2001 Harcourt Publishers Ltd.