<p>The calcium signalling system is important for many cellular processes within the human body. Signals are transmitted within the cell by releasing calcium (Ca<InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="285_2025_2202_Article_IEq1.gif" Format="GIF" Height="11" Rendition="HTML" Resolution="72" Type="Linedraw" Width="17" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{2+}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>2</mn> <mo>+</mo> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation>) from the endoplasmic reticulum (ER) into the cytosol via clusters of Ca<InlineEquation ID="IEq2"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="285_2025_2202_Article_IEq2.gif" Format="GIF" Height="11" Rendition="HTML" Resolution="72" Type="Linedraw" Width="17" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{2+}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>2</mn> <mo>+</mo> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation> channels. Mathematical models of Ca<InlineEquation ID="IEq3"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="285_2025_2202_Article_IEq3.gif" Format="GIF" Height="11" Rendition="HTML" Resolution="72" Type="Linedraw" Width="17" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{2+}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>2</mn> <mo>+</mo> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation> release via inositol 1,4,5-trisphosphate receptors (IP<sub>3</sub>R) are used to compute Ca<InlineEquation ID="IEq4"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="285_2025_2202_Article_IEq4.gif" Format="GIF" Height="11" Rendition="HTML" Resolution="72" Type="Linedraw" Width="17" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{2+}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>2</mn> <mo>+</mo> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation> transients in regions that are difficult to measure directly. In particular, accounting for the data on Ca<InlineEquation ID="IEq5"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="285_2025_2202_Article_IEq5.gif" Format="GIF" Height="11" Rendition="HTML" Resolution="72" Type="Linedraw" Width="17" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{2+}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>2</mn> <mo>+</mo> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation> puffs as stochastic Ca<InlineEquation ID="IEq6"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="285_2025_2202_Article_IEq6.gif" Format="GIF" Height="11" Rendition="HTML" Resolution="72" Type="Linedraw" Width="17" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{2+}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>2</mn> <mo>+</mo> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation> release events in models remains challenging. Parameterising Markov models for representing the IP<sub>3</sub>R with steady-state single channel data obtained at fixed combinations of the ligands Ca<InlineEquation ID="IEq7"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="285_2025_2202_Article_IEq7.gif" Format="GIF" Height="11" Rendition="HTML" Resolution="72" Type="Linedraw" Width="17" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{2+}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>2</mn> <mo>+</mo> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation> and inositol-trisphosphate (IP<sub>3</sub>) has previously been demonstrated to be insufficient. However, by extending an IP<sub>3</sub>R model based on steady-state data with an integral term that incorporates the delayed response of the channel to varying Ca<InlineEquation ID="IEq8"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="285_2025_2202_Article_IEq8.gif" Format="GIF" Height="11" Rendition="HTML" Resolution="72" Type="Linedraw" Width="17" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{2+}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>2</mn> <mo>+</mo> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation> concentrations we succeed in generating realistic Ca<InlineEquation ID="IEq9"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="285_2025_2202_Article_IEq9.gif" Format="GIF" Height="11" Rendition="HTML" Resolution="72" Type="Linedraw" Width="17" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{2+}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>2</mn> <mo>+</mo> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation> puffs. By interpreting the integral term as a weighted average of Ca<InlineEquation ID="IEq10"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="285_2025_2202_Article_IEq10.gif" Format="GIF" Height="11" Rendition="HTML" Resolution="72" Type="Linedraw" Width="17" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{2+}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>2</mn> <mo>+</mo> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation> concentrations that extend over a time interval of length&#xa0;<InlineEquation ID="IEq11"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="285_2025_2202_Article_IEq11.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="11" /> </InlineMediaObject> <EquationSource Format="TEX">\(\tau \)</EquationSource> <EquationSource Format="MATHML"><math> <mi>τ</mi> </math></EquationSource> </InlineEquation> into the past we conclude that the IP<sub>3</sub>R requires a certain amount of memory of past ligand concentrations.</p>

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A Ca2+ puff model based on integrodifferential equations

  • Molly Hawker,
  • Pengxing Cao,
  • Ross A. Kelly,
  • James Sneyd,
  • Ivo Siekmann

摘要

The calcium signalling system is important for many cellular processes within the human body. Signals are transmitted within the cell by releasing calcium (Ca \(^{2+}\) 2 + ) from the endoplasmic reticulum (ER) into the cytosol via clusters of Ca \(^{2+}\) 2 + channels. Mathematical models of Ca \(^{2+}\) 2 + release via inositol 1,4,5-trisphosphate receptors (IP3R) are used to compute Ca \(^{2+}\) 2 + transients in regions that are difficult to measure directly. In particular, accounting for the data on Ca \(^{2+}\) 2 + puffs as stochastic Ca \(^{2+}\) 2 + release events in models remains challenging. Parameterising Markov models for representing the IP3R with steady-state single channel data obtained at fixed combinations of the ligands Ca \(^{2+}\) 2 + and inositol-trisphosphate (IP3) has previously been demonstrated to be insufficient. However, by extending an IP3R model based on steady-state data with an integral term that incorporates the delayed response of the channel to varying Ca \(^{2+}\) 2 + concentrations we succeed in generating realistic Ca \(^{2+}\) 2 + puffs. By interpreting the integral term as a weighted average of Ca \(^{2+}\) 2 + concentrations that extend over a time interval of length  \(\tau \) τ into the past we conclude that the IP3R requires a certain amount of memory of past ligand concentrations.