Calcium-dependent inactivation and the dynamics of calcium puffs and sparks.

Localized intracellular Ca(2+) elevations known as puffs and sparks arise from the cooperative activity of inositol 1,4,5-trisphosphate receptor Ca(2+) channels (IP(3)Rs) and ryanodine receptor Ca(2+) channels (RyRs) clustered at Ca(2+) release sites on the surface of the endoplasmic reticulum or sarcoplasmic reticulum. When Markov chain models of these intracellular Ca(2+)-regulated Ca(2+) channels are coupled via a mathematical representation of a Ca(2+) microdomain, simulated Ca(2+) release sites may exhibit the phenomenon of "stochastic Ca(2+) excitability" reminiscent of Ca(2+) puffs and sparks where channels open and close in a concerted fashion. To clarify the role of Ca(2+) inactivation of IP(3)Rs and RyRs in the dynamics of puffs and sparks, we formulate and analyze Markov chain models of Ca(2+) release sites composed of 10-40 three-state intracellular Ca(2+) channels that are inactivated as well as activated by Ca(2+).

Calcium release site ultrastructure and the dynamics of puffs and sparks.

When Markov chain models of intracellular Ca(2+)-regulated Ca(2+) channels are coupled via a mathematical representation of a Ca(2+) microdomain, simulated Ca(2+) release sites may exhibit the phenomenon of 'stochastic Ca(2+) excitability' reminiscent of Ca(2+) puffs and sparks. Interestingly, some single-channel models that include Ca(2+) inactivation are not particularly sensitive to channel density, so long as the requirement for inter-channel communication is satisfied, while other single-channel models that do not include Ca(2+) inactivation open and close synchronously only when the channel density is in a prescribed range. This observation led us to hypothesize that single-channel models with Ca(2+) inactivation would be less sensitive to the details of release site ultrastructure than models that lack a slow Ca(2+) inactivation process.

Ryanodine receptor allosteric coupling and the dynamics of calcium sparks.

Puffs and sparks are localized intracellular Ca(2+) elevations that arise from the cooperative activity of Ca(2+)-regulated inositol 1,4,5-trisphosphate receptors and ryanodine receptors clustered at Ca(2+) release sites on the surface of the endoplasmic reticulum or the sarcoplasmic reticulum. While the synchronous gating of Ca(2+)-regulated Ca(2+) channels can be mediated entirely though the buffered diffusion of intracellular Ca(2+), interprotein allosteric interactions also contribute to the dynamics of ryanodine receptor (RyR) gating and Ca(2+) sparks. In this article, Markov chain models of Ca(2+) release sites are used to investigate how the statistics of Ca(2+) spark generation and termination are related to the coupling of RyRs via local [Ca(2+)] changes and allosteric interactions.

Feedback inhibition and throughput properties of an integrate-and-fire-or-burst network model of retinogeniculate transmission.

Computational modeling has played an important role in the dissection of the biophysical basis of rhythmic oscillations in thalamus that are associated with sleep and certain forms of epilepsy. In contrast, the dynamic filter properties of thalamic relay nuclei during states of arousal are not well understood. Here we present a modeling and simulation study of the throughput properties of the visually driven dorsal lateral geniculate nucleus (dLGN) in the presence of feedback inhibition from the perigeniculate nucleus (PGN).