Calmodulin (CaM) mutations are associated with congenital long QT (LQT) syndrome (LQTS), which may be related to the dysregulation of the cardiac-predominant Ca2+ channel isoform CaV1.2. Among various mutants, CaM-E141G was identified as a critical missense variant. However, the interaction of this CaM mutant with the CaV1.2 channel has not been determined. In this study, by utilizing a semiquantitative pull-down assay, we explored the interaction of CaM-E141G with CaM-binding peptide fragments of the CaV1.2 channel. Using the patch-clamp technique, we also investigated the electrophysiological effects of the mutant on CaV1.2 channel activity. We found that the maximum binding (Bmax) of CaM-E141G to the proximal COOH-terminal region, PreIQ-IQ, PreIQ, IQ, and NT (an NH2-terminal peptide) was decreased (by 17.71–59.26%) compared with that of wild-type CaM (CaM-WT). In particular, the Ca2+-dependent increase in Bmax became slower with the combination of CaM-E141G + PreIQ and IQ but faster in the case of NT. Functionally, CaM-WT and CaM-E141G at 500 nM Ca2+ decreased CaV1.2 channel activity to 24.88% and 55.99%, respectively, compared with 100 nM Ca2+, showing that the inhibitory effect was attenuated in CaM-E141G. The mean open time of the CaV1.2 channel was increased, and the number of blank traces with no channel opening was significantly decreased. Overall, CaM-E141G exhibits disrupted binding with the CaV1.2 channel and induces a flickering gating mode, which may result in the dysfunction of the CaV1.2 channel and, thus, the development of LQTS. The present study is the first to investigate the detailed binding properties and single-channel gating mode induced by the interaction of CaM-E141G with the CaV1.2 channel.

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In the auction market, allocation and pricing will affect participants’ behavior, honesty, and the success of the auction. A proper mechanism will help to achieve higher utility. In a combinatorial double auction, buyers bidding for commodity combinations of different sellers solve the problem of resource allocation in the real market more efficiently. In view of the problem of allocation and pricing of resource such as cloud resource allocation and spectrum auction, this paper designs the TCD4GB mechanism based on the scene of combined double auction, which determines winners, allocates goods and calculates payments. The concept of unit difference is introduced to this paper in order to solve winner determination problem in the group-buying mechanism. The matched sellers who have the minimum cost is directly chosen to be the winning sellers in the process of selecting the winning buyers. The mechanism also calculates payment by using the unit difference of overlapping buyers and apportion it to the matching sellers through the idea of second-price in VCG mechanism. This mechanism avoids the higher utility of buyers when they report falsely. Through theoretical and simulation experiments, it is proved that the TCD4GB mechanism satisfies the economic attributes of individual rationality and budget balance.

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Group-Buying has becoming a popular commodity trading mode in current business modes. However, the existing unified price of group-buying often determine the price by setting the ladder function according to the final quantities. This method not only ignores the contributions of participants to group-buying, but also cannot overcome the impact of buyers' false reports on group buying mechanism. In this paper, a pricing method of online group-buying based on continuous price function is proposed. We adopt an algorithm called VCG4GB, buyers' payments are the sum of commodities price and the extra amount by purchase quantity. The mechanism motivates buyers to report truthful preference through the compensatory payment. We prove that the mechanism has economic attributes such as incentive compatibility through theoretical proof and simulation experiments.