Dataset Information

Controlling Ca2+-activated K+ channels with models of Ca2+ buffering in Purkinje cells.

ABSTRACT: Intracellular Ca(2+) concentrations play a crucial role in the physiological interaction between Ca(2+) channels and Ca(2+)-activated K(+) channels. The commonly used model, a Ca(2+) pool with a short relaxation time, fails to simulate interactions occurring at multiple time scales. On the other hand, detailed computational models including various Ca(2+) buffers and pumps can result in large computational cost due to radial diffusion in large compartments, which may be undesirable when simulating morphologically detailed Purkinje cell models. We present a method using a compensating mechanism to replace radial diffusion and compared the dynamics of different Ca(2+) buffering models during generation of a dendritic Ca(2+) spike in a single compartment model of a PC dendritic segment with Ca(2+) channels of P- and T-type and Ca(2+)-activated K(+) channels of BK- and SK-type. The Ca(2+) dynamics models used are (1) a single Ca(2+) pool; (2) two Ca(2+) pools, respectively, for the fast and slow transients; (3) detailed Ca(2+) dynamics with buffers, pump, and diffusion; and (4) detailed Ca(2+) dynamics with buffers, pump, and diffusion compensation. Our results show that detailed Ca(2+) dynamics models have significantly better control over Ca(2+)-activated K(+) channels and lead to physiologically more realistic simulations of Ca(2+) spikes and bursting. Furthermore, the compensating mechanism largely eliminates the effect of removing diffusion from the model on Ca(2+) dynamics over multiple time scales.

SUBMITTER: Anwar H

PROVIDER: S-EPMC3411306 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Controlling Ca2+-activated K+ channels with models of Ca2+ buffering in Purkinje cells.

Anwar Haroon H Hong Sungho S De Schutter Erik E

Cerebellum (London, England) 20120901 3

Intracellular Ca(2+) concentrations play a crucial role in the physiological interaction between Ca(2+) channels and Ca(2+)-activated K(+) channels. The commonly used model, a Ca(2+) pool with a short relaxation time, fails to simulate interactions occurring at multiple time scales. On the other hand, detailed computational models including various Ca(2+) buffers and pumps can result in large computational cost due to radial diffusion in large compartments, which may be undesirable when simulati ...[more]

PMID: 20981513

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Project description:Merkel cell-neurite complexes are highly sensitive touch receptors comprising epidermal Merkel cells and sensory afferents. Based on morphological and molecular studies, Merkel cells are proposed to be mechanosensory cells that signal afferents via neurotransmission; however, functional studies testing this hypothesis in intact skin have produced conflicting results. To test this model in a simplified system, we asked whether purified Merkel cells are directly activated by mechanical stimulation. Cell shape was manipulated with anisotonic solution changes and responses were monitored by Ca2+ imaging with fura-2. We found that hypotonic-induced cell swelling, but not hypertonic solutions, triggered cytoplasmic Ca2+ transients. Several lines of evidence indicate that these signals arise from swelling-activated Ca2+-permeable ion channels. First, transients were reversibly abolished by chelating extracellular Ca2+, demonstrating a requirement for Ca2+ influx across the plasma membrane. Second, Ca2+ transients were initially observed near the plasma membrane in cytoplasmic processes. Third, voltage-activated Ca2+ channel (VACC) antagonists reduced transients by half, suggesting that swelling-activated channels depolarize plasma membranes to activate VACCs. Finally, emptying internal Ca2+ stores attenuated transients by 80%, suggesting Ca2+ release from stores augments swelling-activated Ca2+ signals. To identify candidate mechanotransduction channels, we used RT-PCR to amplify ion-channel transcripts whose pharmacological profiles matched those of hypotonic-evoked Ca2+ signals in Merkel cells. We found 11 amplicons, including PKD1, PKD2, and TRPC1, channels previously implicated in mechanotransduction in other cells. Collectively, these results directly demonstrate that Merkel cells are activated by hypotonic-evoked swelling, identify cellular signaling mechanisms that mediate these responses, and support the hypothesis that Merkel cells contribute to touch reception in the Merkel cell-neurite complex.

Dataset Information

Controlling Ca2+-activated K+ channels with models of Ca2+ buffering in Purkinje cells.

Publications

Controlling Ca2+-activated K+ channels with models of Ca2+ buffering in Purkinje cells.

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