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 (PMCA). PMCA variability is increased by the presence of two splicing sites. Functional differences between the variants of PMCA have been described, but little is known about the adaptive advantages of this great diversity of pumps. In this paper we studied how the different isoforms respond to a sudden increase in Ca2+ concentration. We found that different PMCAs are activated by Ca2+ at different rates, PMCA 3f and 2a being the fastest, and 4b the slowest. The rate of activation by Ca2+ depends both on the rate of calmodulin binding and the magnitude of the activation by calmodulin. We found that 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 Ca2+ peak, while in Jurkat cells the recovery takes up to a minute. In stereocilia, 2a is the only method for export of Ca2+, making the analysis of them unusually straightforward. This indicates that these rates of PMCA activation by Ca2+ are correlated with the speed of Ca2+ concentration decay after 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 the speed of Ca2+ signals in the cell. (C) 2001 Harcourt Publishers Ltd.