In skeletal muscle excitation–contraction (E–C) coupling, the depolarization signal is converted from the intracellular Ca2+ store into Ca2+ release by functional coupling between the cell surface voltage sensor and the Ca2+ release channel on the sarcoplasmic reticulum (SR). The signal conversion occurs in the junctional membrane complex known as the triad junction, where the invaginated plasma membrane called the transverse-tubule (T-tubule) is pinched from both sides by SR membranes. Previous studies have suggested that junctophilins (JPs) contribute to the formation of the junctional membrane complexes by spanning the intracellular store membrane and interacting with the plasma membrane (PM) in excitable cells. Of the three JP subtypes, both type 1 (JP-1) and type 2 (JP-2) are abundantly expressed in skeletal muscle. To examine the physiological role of JP-1 in skeletal muscle, we generated mutant mice lacking JP-1. The JP-1 knockout mice showed no milk suckling and died shortly after birth. Ultrastructural analysis demonstrated that triad junctions were reduced in number, and that the SR was often structurally abnormal in the skeletal muscles of the mutant mice. The mutant muscle developed less contractile force (evoked by low-frequency electrical stimuli) and showed abnormal sensitivities to extracellular Ca2+. Our results indicate that JP-1 contributes to the construction of triad junctions and that it is essential for the efficiency of signal conversion during E–C coupling in skeletal muscle.
The dispersion copolymerization of n-butyl methacrylate (BMA) in methanol-water media has been investigated. The reactions were carried out in the presence of a series of poly(ethylene oxide) (PEO) macromonomers(1) (Ci-EO"-(CH2)m-S), with a p-alkylstyrene (S) end group, with m = 1,4, and 7 and = 53 and 110. Nearly monodisperse PBMA latex particles from 90 to 500 nm in diameter are obtained. Factors which affect the particle size are the structure and molecular weight of the macromonomers, initial BMA, initiator, and macromonomer concentrations, temperature, and the composition of the solvent. The particle radius (R) follows the relationship R = [ ] 0•82±0 06-[macromonomer]o_0 54±0 03n_0 30±0 02[initiator]o_010±0 01. The power law exponents are close to those predicted from a coagulative nucleation model, particularly the multibin kinetics model for coalescence among unstabilized particles developed by Paine [Macromolecules 1990, 23, 3109]. R is also found to decrease with an increase in temperature and also with an increase in m (in 1). R, however, also increases with an increasing volume fraction of water in the reaction medium. The mechanism for the dispersion copolymerization is discussed in detail.
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