Calcium diffusion modeling in a spherical neuron. Relevance of buffering properties

Abstract

We have developed a calcium diffusion model for a spherical neuron which incorporates calcium influx and extrusion through the plasma membrane as well as three calcium buffer systems with different capacities, mobilities, and kinetics. The model allows us to calculate the concentration of any of the species involved at all locations in the cell and can be used to account for experimental data obtained with high-speed Ca imaging techniques. The influence of several factors on the Ca2+ transients is studied. The relationship between peak [Ca2+]i and calcium load is shown to be nonlinear and to depend on buffer characteristics. The time course of the Ca2+ signals is also shown to be dependent on buffer properties. In particular, buffer mobility strongly determines the size and time course of Ca2+ signals in the cell interior. The model predicts that the presence of exogenous buffer, such as fura-2, modifies the Ca2+ transients to a variable extent depending on its proportion relative to the natural, intrinsic buffers. The conclusions about natural calcium buffer properties that can be derived from Ca imaging experiments are discussed.

Ca2+from One or Two Channels Controls Fusion of a Single Vesicle at the Frog Neuromuscular Junction

“…This is equivalent to buffer capacities of up to 250. We did not consider any Ca 2ϩ extrusion, sequestration, or release from internal stores, because their contribution to [Ca 2ϩ ] profiles for short time intervals (ϳ1 ms) is negligible (Sala and Hernandez-Cruz, 1990). …”

Short-Term Changes in the Ca2+-Exocytosis Relationship during Repetitive Pulse Protocols in Bovine Adrenal Chromaffin Cells

“…Pulsatile C a 2ϩ entry during a train will create very different submembrane [C a 2ϩ ] profiles than will a continuous long depolarization (Sala and Hernandez-Cruz, 1990;Nowycky and Pinter, 1993;K lingauf and Neher, 1997). As was emphasized in Engisch and Now ycky (1996), the standard transfer function does not relate exocytosis to submembrane [C a 2ϩ ], but simply serves as a predictor for the total exocytosis expected for a given amount of C a 2ϩ entry.…”

[Ca2+]iElevations Detected by BK Channels during Ca2+Influx and Muscarine-Mediated Release of Ca2+from Intracellular Stores in Rat Chromaffin Cells

“…Although these buffers can monitor changes in bulk [Ca 2ϩ ] i that follow physiological stimuli, limitations in the methods used to detect fluorescent signals make it difficult to follow the localized Ca 2ϩ gradients predicted to occur near individual Ca 2ϩ channels. Furthermore, introduction of these exogenous buffers alters many features of the [Ca 2ϩ ] i elevations (Sala and Hernandez-Cruz, 1990;Zhou and Neher, 1993). Therefore, there is increasing interest in using intrinsic Ca 2ϩ -dependent proteins or processes to define the amplitudes and time course of [Ca 2ϩ ] i elevations.…”