Membrane-initiated Ca2+ signals are reshaped during propagation to subcellular regions

An important aspect of Ca2+ signaling is the ability of cells to generate intracellular Ca2+ waves. In this study we have analyzed the cellular and subcellular kinetics of Ca2+ waves in a neuroendocrine transducer cell, the melanotrope of Xenopus laevis, using the ratiometric Ca2+ probe indo-1 and video-rate UV confocal laser-scanning microscopy. The purpose of the present study was to investigate how local Ca2+ changes contribute to a global Ca2+ signal; subsequently we quantified how a Ca2+ wave is kinetically reshaped as it is propagated through the cell. The combined kinetics of all subcellular Ca2+ signals determined the shape of the total cellular Ca2+ signal, but each subcellular contribution to the cellular signal was not constant in time. Near the plasma membrane, [Ca2+](i) increased and decreased rapidly, processes that can be described by a linear and exponential function, respectively. In more central parts of the cell slower kinetics were observed that were best described by a Hill equation. This reshaping of the Ca2+ wave was modeled with an equation derived from a low-pass RC filter. We propose that the differences in spatial kinetics of the Ca2+ signal serves as a mechanism by which the same cellular Ca2+ signal carries different regulatory information to different subcellular regions of the cell, thus evoking differential cellular responses.