title: Stochastic amplification of calcium-activated potassium currents in Ca2+ microdomains.
abstract: Small conductance (SK) calcium-activated potassium channels are found in many tissues throughout the body and open in response to elevations in intracellular calcium. In hippocampal neurons, SK channels are spatially co-localized with L-Type calcium channels. Due to the restriction of calcium transients into microdomains, only a limited number of L-Type Ca(2+) channels can activate SK and, thus, stochastic gating becomes relevant. Using a stochastic model with calcium microdomains, we predict that intracellular Ca(2+) fluctuations resulting from Ca(2+) channel gating can increase SK2 subthreshold activity by 1-2 orders of magnitude. This effectively reduces the value of the Hill coefficient. To explain the underlying mechanism, we show how short, high-amplitude calcium pulses associated with stochastic gating of calcium channels are much more effective at activating SK2 channels than the steady calcium signal produced by a deterministic simulation. This stochastic amplification results from two factors: first, a supralinear rise in the SK2 channel's steady-state activation curve at low calcium levels and, second, a momentary reduction in the channel's time constant during the calcium pulse, causing the channel to approach its steady-state activation value much faster than it decays. Stochastic amplification can potentially explain subthreshold SK2 activation in unified models of both sub- and suprathreshold regimes. Furthermore, we expect it to be a general phenomenon relevant to many proteins that are activated nonlinearly by stochastic ligand release.
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287, USA. davearthur.stanley@gmail.com
authors.forename: David Arthur
authors.initials: DA
authors.lastname: Stanley
authors.forename: Berj L
authors.initials: BL
authors.lastname: Bardakjian
authors.forename: Mark L
authors.initials: ML
authors.lastname: Spano
authors.forename: William L
authors.initials: WL
authors.lastname: Ditto
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D021962:Membrane Microdomains / Q000502:physiology*; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D013269:Stochastic Processes
chemical_list: D051640:Small-Conductance Calcium-Activated Potassium Channels