Oxidative folding facilitates protein import into the mitochondrial intermembrane space. An analysis of the process in intact mammalian cells reveals the contributions of Mia40, ALR, glutathione, and the membrane potential. Proteins that rely on oxidative folding remain stable and reduced in the cytosol for several minutes.

Pretreatment of both MB and SB with DEB failed to show angiographic and clinical superiority over conventional BMS, using a provisional T-stenting technique. Moreover DES showed superior angiographic results than DEB and BMS.

Summary Multiple sclerosis (MS) is a demyelinating disease caused by an auto-reactive immune system. Recent studies also demonstrated synapse dysfunctions in MS patients and MS mouse models. We previously observed decreased synaptic vesicle exocytosis in photoreceptor synapses in the EAE mouse model of MS at an early, preclinical stage. In the present study, we analyzed whether synaptic defects are associated with altered presynaptic Ca 2+ signaling. Using high-resolution immunolabeling, we found a reduced signal intensity of Cav-channels and RIM2 at active zones in early, preclinical EAE. In line with these morphological alterations, depolarization-evoked increases of presynaptic Ca 2+ were significantly smaller. In contrast, basal presynaptic Ca 2+ was elevated. We observed a decreased expression of Na + /K + -ATPase and plasma membrane Ca 2+ ATPase 2 (PMCA2), but not PMCA1, in photoreceptor terminals of EAE mice that could contribute to elevated basal Ca 2+ . Thus, complex Ca 2+ signaling alterations contribute to synaptic dysfunctions in photoreceptors in early EAE.

β-Adrenergic stimulation enhances Ca currents via L-type, voltage-gated Ca 1.2 channels, strengthening cardiac contraction. The signalling via β-adrenergic receptors (β-ARs) involves elevation of cyclic AMP (cAMP) levels and activation of protein kinase A (PKA). However, how PKA affects the channel remains controversial. Recent studies in heterologous systems and genetically engineered mice stress the importance of the post-translational proteolytic truncation of the distal C-terminus (dCT) of the main (α ) subunit. Here, we successfully reconstituted the cAMP/PKA regulation of the dCT-truncated Ca 1.2 in Xenopus oocytes, which previously failed with the non-truncated α . cAMP and the purified catalytic subunit of PKA, PKA-CS, injected into intact oocytes, enhanced Ca 1.2 currents by ∼40% (rabbit α ) to ∼130% (mouse α ). PKA blockers were used to confirm specificity and the need for dissociation of the PKA holoenzyme. The regulation persisted in the absence of the clipped dCT (as a separate protein), the A kinase-anchoring protein AKAP15, and the phosphorylation sites S1700 and T1704, previously proposed as essential for the PKA effect. The Ca β subunit was not involved, as suggested by extensive mutagenesis. Using deletion/chimeric mutagenesis, we have identified the initial segment of the cardiac long-N-terminal isoform of α as a previously unrecognized essential element involved in PKA regulation. We propose that the observed regulation, that exclusively involves the α subunit, is one of several mechanisms underlying the overall PKA action on Ca 1.2 in the heart. We hypothesize that PKA is acting on Ca 1.2, in part, by affecting a structural 'scaffold' comprising the interacting cytosolic N- and C-termini of α .

PPCI by DEB-only in selected patients yielded an angiographic outcome comparable to BMS alone and DEB followed by BMS. PES proved angiographic superiority to DEB-only. DEB-only is therefore a potential treatment alternative during PPCI in patients with contra-indications to drug-eluting stents.