Simulation of Spontaneous Ca2+ Oscillations in Astrocytes Mediated by Voltage-Gated Calcium Channels

Abstract

The purpose of this computational study was to investigate the possible role of voltage-gated Ca(2+) channels in spontaneous Ca(2+) oscillations of astrocytes. By incorporating different types of voltage-gated Ca(2+) channels and a previous model, this study reproduced typical Ca(2+) oscillations in silico. Our model could mimic the oscillatory phenomenon under a wide range of experimental conditions, including resting membrane potential (-75 to -60 mV), extracellular Ca(2+) concentration (0.1 to 1500 muM), temperature (20 to 37 degrees C), and blocking specific Ca(2+) channels. By varying the experimental conditions, the amplitude and duration of Ca(2+) oscillations changed slightly (both<25%), while the frequency changed significantly ( approximately 400%). This indicates that spontaneous Ca(2+) oscillations in astrocytes might be an all-or-none process, which might be frequency-encoded in signaling. Moreover, the properties of Ca(2+) oscillations were found to be related to the dynamics of Ca(2+) influx, and not only to a constant influx. Therefore, calcium channels dynamics should be used in studying Ca(2+) oscillations. This work provides a platform to explore the still unclear mechanism of spontaneous Ca(2+) oscillations in astrocytes.

Modeling the spontaneousCa2+oscillations in astrocytes: Inconsistencies and usefulness

“…Astrocytes in rat brains expressed mainly the type 2 IP 3 Rs (Sharp et al, 1999;Holtzclaw et al, 2002). Recently, an empirically based model has been proposed for this particular IP 3 Rs isoform (Tu et al, 2005a,b), which seems very useful to portray Ca 2þ signaling in astrocytes (Lavrentovich & Hemkin, 2008;Zeng et al, 2009). In spite of the accuracy of these latterly proposed models for type 2 IP 3 Rs, it is our believe that the Li-Rinzel's simplified model not only captures the most important characteristics in the kinetics of the IP 3 R, but also can be directly interpreted in terms of molecular transitions in the receptor states (i.e., the subunits).…”

“…Previous studies have also demonstrated the existence of voltage-gated and ligand/storeoperated forms of active influxes. For example, different types of voltage-dependent Ca 2þ channels have been found in astrocytes (D'Ascenzo et al, 2004), a mechanism that was contemplated in a recent theoretical model (Zeng et al, 2009). However, blocking these voltage-gated Ca 2þ channels has produced different effects on the SCOs in astrocytes (Parri et al, 2001;Aguado et al, 2002;Wang et al, 2006b).…”

“…IP 4 ) There is not Ca 2þ feedback on the IP 3 R Ca 2þ oscillations are necessarily accompanied by IP 3 oscillations models for Ca 2þ signaling in astrocytes have included an IP 3 production mechanism through a PLC enzyme; thus, they classify as models of a third class. Some of these previous models included a simple Ca 2þ modulatory feedback regulating the PLC 1 enzyme (H€ ofer et al, 2002;Goto et al, 2004;Ullah et al, 2006;Di Garbo et al, 2007;Lavrentovich & Hemkin, 2008;Zeng et al, 2009), but others comprised mechanisms involving additionally purinergic signals (Stamatakis & Mantzaris, 2006) and the activity of PKC complexes (Kang & Othmer, 2009). Even rarely, the first class of models has been used in the past to explain astrocytic Ca 2þ signaling (Bennett et al, 2008).…”

“…A variety of biophysical models have been used in the past to interpret ROI-based epifluorescent data observed in cerebral astrocytes, in particular from their cellular somata (Ullah et al, 2006;Lavrentovich & Hemkin, 2008;Zeng et al, 2009;Riera et al, 2011). In other cases, these models have been used to explain the spatiotemporal characteristics of intracellular and intercellular (H€ ofer et al, 2002;Goto et al, 2004;Stamatakis & Mantzaris, 2006;Kang & Othmer, 2009;Wei & Shuai, 2011) Ca 2þ signaling in astrocytes.…”

Two dimensional finite element estimation of calcium ions in presence fo NCX and Buffers in Astrocytes

“…Previous researcher have studied the effect of rapid and excess buffers on cytosolic calcium concentration in nerve cells like neuron, astrocytes, fibrocytes etc [3,4,5,9,10,12,15,17,19,21]. Calcium kinetics in nerve cells is governed by a set of reaction-diffusion equations which can be framed assuming the following bimolecular reaction between [Ca 2+ ] and buffer species [11,12]:…”