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.