Increased ventricular loading reduced longitudinal shortening (P = .01) and shortened ARI (P = .02), but changes were heterogeneous between cardiac segments. Increased regional longitudinal shortening was associated with ARI shortening (effect size 0.20 [0.01-0.38] ms/%; P = .04) and increased local ARI dispersion (effect size -0.13 [-0.23 to -0.03] ms/%; P = .04). At the whole organ level, increased mechanical dispersion translated into increased dispersion of repolarization (correlation coefficient r = 0.81; P = .01). Mechanoelectric feedback can establish a potentially proarrhythmic substrate in the human heart and should be considered to advance our understanding and prevention of cardiac arrhythmias.Mechanoelectric feedback can establish a potentially proarrhythmic substrate in the human heart and should be considered to advance our understanding and prevention of cardiac arrhythmias. The optimal strategy for catheter ablation of persistent atrial fibrillation (PeAF) remains unknown. A preprocedural additive treatment for patients undergoing pulmonary vein isolation (PVI) alone to optimize catheter ablation should be investigated. The purpose of this study was to determine whether pharmacologic cardioversion with a fixed low-dose antiarrhythmic drug (AAD) before ablation could stratify the long-term outcome of a PVI-alone strategy. We conducted a prospective cohort study of PeAF patients who underwent PVI using contact force-sensing catheters. No substrate modification was performed. Fixed low-dose bepridil was administered before ablation for cardioversion and patients were classified into 2 groups based on obtaining sinus rhythm (SR). The rate of recurrence of atrial fibrillation (AF) and/or atrial tachycardia (AT) within 36 months was compared between the 2 groups. Among the 303 PeAF patients who received the AAD, 102 returned to SR (SR group), and the other 201 had persistence of AF (non-SR group). AF persistence duration at baseline and during bepridil administration was similar between the 2 groups. The SR group had a significantly lower 36-month AF/AT recurrence rate than the non-SR group (17 [22.2%] vs 55 [34.0%], log-rank P = .022). AT-type recurrence was observed in 16 patients (2 [3.3%] in the SR group vs 14 [8.9%] in the non-SR group; log-rank P = .051). Nonresponse to AAD was an independent predictor of AF/AT recurrence after adjusting for other risk factors (hazard ratio 1.34; 95% confidence interval 1.01-1.77; P = .040). Preprocedural pharmacologic cardioversion could be a useful determinant for patients with treatable PeAF by PVI alone.Preprocedural pharmacologic cardioversion could be a useful determinant for patients with treatable PeAF by PVI alone. Transport of Ca into pancreatic β cell mitochondria facilitates nutrient-mediated insulin secretion. However, the underlying mechanism is unclear. Recent establishment of the molecular identity of the mitochondrial Ca uniporter (MCU) and associated proteins allows modification of mitochondrial Ca transport in intact cells. We examined the consequences of deficiency of the accessory protein MICU2 in rat and human insulin-secreting cells and mouse islets. siRNA silencing of Micu2 in the INS-1 832/13 and EndoC-βH1 cell lines was performed; Micu2 mice were also studied. Insulin secretion and mechanistic analyses utilizing live confocal imaging to assess mitochondrial function and intracellular Ca dynamics were performed. Silencing of Micu2 abrogated GSIS in the INS-1 832/13 and EndoC-βH1 cells. The Micu2 mice also displayed attenuated GSIS. Mitochondrial Ca uptake declined in MICU2-deficient INS-1 832/13 and EndoC-βH1 cells in response to high glucose and high K . MICU2 silencing in INS-1 832 compartment, preventing desensitization of voltage-dependent Ca2+ channels and facilitating GSIS.Cholesterol, an essential lipid for cell signaling and structural integrity of cellular membranes, is highly enriched in the plasma membrane (PM). However, the regulatory mechanisms that control its biosynthesis and uptake both reside in the endoplasmic reticulum (ER). mTOR peptide Thus, the ER needs to constantly monitor the levels of PM cholesterol. This is in part mediated by regulated transport of a biochemically defined pool of cholesterol, termed "accessible" cholesterol, from the PM to the ER via evolutionarily conserved ER-anchored lipid transfer proteins, the GRAMD1s/Asters (GRAMD1a/1b/1c) (Lam/Ltc proteins in yeast). GRAMD1s possess cytosolically exposed GRAM domain and StART-like domain followed by a transmembrane ER anchor. They form homo- and hetero-meric complexes and move to the contacts formed between the ER and the PM by sensing a transient expansion of the accessible pool of cholesterol in the PM via the GRAM domain and facilitate its extraction and transport to the ER via the StART-like domain. The GRAMD1b GRAM domain possesses distinct, but synergistic sites, for recognizing accessible cholesterol and anionic lipids, including phosphatidylserine, within the PM. This property of the GRAM domain contributes to regulated tethering of the PM to ER membrane where GRAMD1s are anchored and fine-tunes StART-like domain-dependent accessible cholesterol transport. Thus, cells use GRAMD1s to sense the levels of cholesterol in the PM and regulate transport of accessible PM cholesterol to the ER in order to maintain cholesterol homeostasis.Autophagy, an intracellular degradation mechanism, involves de novo generation of autophagosomes that sequester and deliver cytoplasmic components to the lysosome for degradation. The mechanism behind autophagosomal membrane expansion has been a longstanding enigma in this field. Recent structural and biochemical analyses have revealed that two mysterious autophagy-related (Atg) proteins, Atg2 and Atg9, are novel types of intermembrane and interleaflet lipid transporters, respectively. This review summarizes recent discoveries surrounding Atg2 and Atg9 as a lipid transporter and discusses the molecular mechanism of autophagosomal membrane expansion driven by collaboration between these two lipid transporters.Transporters expressed by hepatocytes and enterocytes play a critical role in maintaining the enterohepatic circulation of bile acids. The sodium taurocholate cotransporting polypeptide (NTCP), exclusively expressed at the basolateral side of hepatocytes, mediates the uptake of conjugated bile acids. In conditions where bile flow is impaired (cholestasis), pharmacological inhibition of NTCP-mediated bile acid influx is suggested to reduce hepatocellular damage due to bile acid overload. Furthermore, NTCP has been shown to play an important role in hepatitis B virus (HBV) and hepatitis Delta virus (HDV) infection by functioning as receptor for viral entry into hepatocytes. This review provides a summary of current molecular insight into the regulation of NTCP expression at the plasma membrane, hepatic bile acid transport, and NTCP-mediated viral infection.