Population Density and Moment-based Approaches to Modeling Domain Calcium-mediated Inactivation of L-type Calcium Channels

Acta Biotheoretica 64 (1):11-32 (2016)

Authors
Abstract
We present a population density and moment-based description of the stochastic dynamics of domain $${\text{Ca}}^{2+}$$ Ca 2 + -mediated inactivation of L-type $${\text{Ca}}^{2+}$$ Ca 2 + channels. Our approach accounts for the effect of heterogeneity of local $${\text{Ca}}^{2+}$$ Ca 2 + signals on whole cell $${\text{Ca}}^{2+}$$ Ca 2 + currents; however, in contrast with prior work, e.g., Sherman et al. :985–995, 1990), we do not assume that $${\text{Ca}}^{2+}$$ Ca 2 + domain formation and collapse are fast compared to channel gating. We demonstrate the population density and moment-based modeling approaches using a 12-state Markov chain model of an L-type $${\text{Ca}}^{2+}$$ Ca 2 + channel introduced by Greenstein and Winslow :2918–2945, 2002). Simulated whole cell voltage clamp responses yield an inactivation function for the whole cell $${\text{Ca}}^{2+}$$ Ca 2 + current that agrees with the traditional approach when domain dynamics are fast. We analyze the voltage-dependence of $${\text{Ca}}^{2+}$$ Ca 2 + inactivation that may occur via slow heterogeneous domain [ $${\text{Ca}}^{2+}$$ Ca 2 + ]. Next, we find that when channel permeability is held constant, $${\text{Ca}}^{2+}$$ Ca 2 + -mediated inactivation of L-type channels increases as the domain time constant increases, because a slow domain collapse rate leads to increased mean domain [ $${\text{Ca}}^{2+}$$ Ca 2 + ] near open channels; conversely, when the maximum domain [ $${\text{Ca}}^{2+}$$ Ca 2 + ] is held constant, inactivation decreases as the domain time constant increases. Comparison of simulation results using population densities and moment equations confirms the computational efficiency of the moment-based approach, and enables the validation of two distinct methods of truncating and closing the open system of moment equations. In general, a slow domain time constant requires higher order moment truncation for agreement between moment-based and population density simulations.
Keywords No keywords specified (fix it)
Categories (categorize this paper)
ISBN(s)
DOI 10.1007/s10441-015-9271-y
Options
Edit this record
Mark as duplicate
Export citation
Find it on Scholar
Request removal from index
Revision history

Download options

Our Archive


Upload a copy of this paper     Check publisher's policy     Papers currently archived: 40,736
External links

Setup an account with your affiliations in order to access resources via your University's proxy server
Configure custom proxy (use this if your affiliation does not provide a proxy)
Through your library

References found in this work BETA

No references found.

Add more references

Citations of this work BETA

No citations found.

Add more citations

Similar books and articles

Modulation of the cGMP-Gated Channel by Calcium.Mandeep S. Sagoo & Leon Lagnado - 1995 - Behavioral and Brain Sciences 18 (3):486-486.
A Domain of Unital Channels.Johnny Feng - 2012 - Foundations of Physics 42 (7):959-975.

Analytics

Added to PP index
2016-06-30

Total views
7 ( #851,366 of 2,243,784 )

Recent downloads (6 months)
1 ( #1,042,515 of 2,243,784 )

How can I increase my downloads?

Downloads

My notes

Sign in to use this feature