Date Thesis Awarded
Honors Thesis -- Open Access
Bachelors of Science (BS)
Gregory D. Smith
Lawrence M. Leemis
We present a minimal whole cell model of stochastic domain Ca mediated inactivation of low-density L-type Ca channels. Our approach avoids the computationally demanding task of resolving spatial aspects of global Ca signaling by using probability densities and associated moment equations to represent heterogeneous local Ca signals (Williams et al. Biophys J. 92(7):2311-28, 2007; Biophys J. 95(4):1689-703, 2008). Using a minimal Markov chain model of an L-type Ca channel, simulated whole cell responses to a two-pulse voltage clamp protocol yield an inactivation function for the whole cell Ca current that deviates from that obtained by assuming instantaneous formation and collapse of Ca domains, as in the domain-mediated Ca inactivation model introduced by Sherman, Keizer, and Rinzel (1990). Parameter studies reveal that when domain Ca formation and collapse are slow compared to channel kinetics (e.g., fast voltage-dependent gating), and the maximum domain concentration is held constant, inactivation in the high-voltage regime is attenuated. When the domain dynamics are slow compared to channel kinetics, and the channel permeability is held constant, inactivation is augmented for all voltages. We also derive an open system of moment equations as well as present a suggestion for moment closure that may facilitate analysis and simulation of domain Ca mediated inactivation of low-density L-type Ca channels.
Hardcastle, Kiah, "A Population Density Model of Domain Calcium-Mediated Inactivation of L-Type Ca Channels" (2013). Undergraduate Honors Theses. William & Mary. Paper 623.
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