Mathematical modeling of mechanisms underlying ACh-induced [Ca2+]i oscillations in tracheal smooth muscle

M. G. Aguayo, Y.s. Prakash, M. S. Kannan, Gary C Sieck

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Abstract

In porcine tracheal smooth muscle (TSM) cells, ACh induces [Ca2+]i oscillations, which reflect Ca2+ release through ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR). These ACh-induced [Ca2+]i oscillations display an initial period of faster oscillations followed by a slower steady state phase. This biphasic pattern may reflect either the dynamic release kinetics of RyR channels (one-compartment model) or the interactive influence of RyR mediated Ca2+ release and other Ca2+ regulatory mechanisms (two-compartment model). These alternative models were simulated under 2 experimental conditions: 1) intact TSM cells, where all Ca2+ regulatory mechanisms were present, and 2) β-escin permeabilized cells where the influence of Ca2+ influx and efflux was eliminated. Initial model parameters were constrained based on previously reported values. We found that a two-compartment model best fits the biphasic pattern of ACh-induced [Ca2+]i oscillations in intact TSM cells, consistent with the involvement of more than RyR channels. When the influence of Ca2+ influx and efflux were removed in β-escin permeabilized TSM cells, ACh-induced [Ca2+]i oscillations could be modeled by one-compartment. Similarly, a one-compartment model adequately represented the steady state phase of ACh-induced [Ca2+]i oscillations. We conclude that dynamic modulation of ACh-induced [Ca2+]i oscillations involves Ca2+ regulatory mechanisms other than RyR mediated Ca2+ release.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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