Membrane-Initiated Ca 2+ Signals Are Reshaped during Propagation to Subcellular Regions

Abstract

An important aspect of Ca 2+ signaling is the ability of cells to generate intracellular Ca 2+ waves. In this study we have analyzed the cellular and subcellular kinetics of Ca 2+ waves in a neuroendocrine transducer cell, the melanotrope of Xenopus laevis, using the ratiometric Ca 2+ probe indo-1 and video-rate UV confocal laser-scanning microscopy. The purpose of the present study was to investigate how local Ca 2+ changes contribute to a global Ca 2+ signal; subsequently we quantified how a Ca 2+ wave is kinetically reshaped as it is propagated through the cell. The combined kinetics of all subcellular Ca 2+ signals determined the shape of the total cellular Ca 2+ signal, but each subcellular contribution to the cellular signal was not constant in time. Near the plasma membrane, [Ca 2+] 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 Ca 2+ wave was modeled with an equation derived from a low-pass RC filter. We propose that the differences in spatial kinetics of the Ca 2+ signal serves as a mechanism by which the same cellular Ca 2+ signal carries different regulatory information to different subcellular regions of the cell, thus evoking differential cellular responses.