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- W1967159944 abstract "Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays an important role in L-type Ca(2+) channel (LCC) facilitation: the Ca(2+)-dependent augmentation of Ca(2+) current (I(CaL)) exhibited during rapid repeated depolarization. Multiple mechanisms may underlie facilitation, including an increased rate of recovery from Ca(2+)-dependent inactivation and a shift in modal gating distribution from mode 1, the dominant mode of LCC gating, to mode 2, a mode in which openings are prolonged. We hypothesized that the primary mechanism underlying facilitation is the shift in modal gating distribution resulting from CaMKII-mediated LCC phosphorylation. We developed a stochastic model describing the dynamic interactions among CaMKII, LCCs, and phosphatases as a function of dyadic Ca(2+) and calmodulin levels, and we incorporated it into an integrative model of the canine ventricular myocyte. The model reproduces behaviors at physiologic protein levels and allows for dynamic transition between modes, depending on the LCC phosphorylation state. Simulations showed that a CaMKII-dependent shift in LCC distribution toward mode 2 accounted for the I(CaL) positive staircase. Moreover, simulations demonstrated that experimentally observed changes in LCC inactivation and recovery kinetics may arise from modal gating shifts, rather than from changes in intrinsic inactivation properties. The model therefore serves as a powerful tool for interpreting I(CaL) experiments." @default.
- W1967159944 created "2016-06-24" @default.
- W1967159944 creator A5006612116 @default.
- W1967159944 creator A5027197038 @default.
- W1967159944 creator A5085871644 @default.
- W1967159944 date "2009-03-01" @default.
- W1967159944 modified "2023-10-12" @default.
- W1967159944 title "CaMKII-Induced Shift in Modal Gating Explains L-Type Ca2+ Current Facilitation: A Modeling Study" @default.
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- W1967159944 doi "https://doi.org/10.1016/j.bpj.2008.11.055" @default.
- W1967159944 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2717283" @default.
- W1967159944 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19254537" @default.
- W1967159944 hasPublicationYear "2009" @default.
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