Mutations in the pancreatic ATP-sensitive potassium (K(ATP)) channel subunits sulfonylurea receptor 1 (SUR1) and the inwardly rectifying potassium channel Kir6.2 cause persistent hyperinsulinemic hypoglycemia of infancy. We have identified a SUR1 mutation, L1544P, in a patient with the disease. Channels formed by co-transfection of Kir6.2 and the mutant SUR1 in COS cells have reduced response to MgADP ( approximately 10% that of the wild-type channels) and reduced surface expression ( approximately 19% that of the wild-type channels). However, the steady-state level of the SUR1 protein is unaffected. Treating cells with lysosomal or proteasomal inhibitors did not improve surface expression of the mutant channels, suggesting that increased degradation of mutant channels by either pathway is unlikely to account for the reduced surface expression. Removal of the RKR endoplasmic reticulum retention/retrieval trafficking motif in either SUR1 or Kir6.2 increased the surface expression of the mutant channel by approximately 35 and approximately 20%, respectively. The simultaneous removal of the RKR motif in both channel subunits restored surface expression of the mutant channel to the wild-type channel levels. Thus, the L1544P mutation may interfere with normal trafficking of K(ATP) channels by causing improper shielding of the RKR endoplasmic reticulum retention/retrieval trafficking signals in the two channel subunits.

This cross-sectional comparative study investigated the levels of insomnia, anxiety, and heart rate variability of nurses members working different shift systems. One hundred and twenty-four participants were recruited from members of the nurses of two Taiwanese hospitals. Data were collected using the Chinese versions of the Athens Insomnia Scale and Beck Anxiety Scale questionnaires and electrocardiograms recorded immediately upon completion of each participant's work shift. A binary logistic regression model was used for analysis. Insomnia, anxiety, and abnormal parasympathetic activity were more acute in nurses who worked a rotating shift than in those performing day or night shift work. Logistic regression analysis showed that age significantly increased the incidence and level of insomnia. Age, years of service, and nurses' status as a parent significantly intensified incidences of anxiety and abnormal parasympathetic activity. Rotating shift work is one of the main factors causing adverse effects on the physical and psychological health of nurses; therefore, when a shift work system cannot be avoided, a practice of day and night shifts for nurses is preferable to rotating shifts.

Evidence from this study validated the multisensory stimulation therapy protocol. Therefore, this protocol may be incorporated into clinical interventions to improve quality of care and to alleviate the negative emotions of patients with chronic schizophrenia.

Mutations in the sulfonylurea receptor 1 (SUR1), a subunit of ATP-sensitive potassium (K ATP ) channels, cause familial hyperinsulinism. One such mutation, deletion of phenylalanine 1388 (⌬Phe-1388), leads to defects in both trafficking and MgADP response of K ATP channels. Here we investigated the biochemical features of Phe-1388 that control the proper trafficking and function of K ATP channels by substituting the residue with all other 19 amino acids. Whereas surface expression is largely dependent on hydrophobicity, channel response to MgADP is governed by multiple factors and involves the detailed architecture of the amino acid side chain. Thus, structural features in SUR1 required for proper channel function are distinct from those required for correct protein trafficking. Remarkably, replacing Phe-1388 by leucine profoundly alters the physiological and pharmacological properties of the channel. The F1388L-SUR1 channel has increased sensitivity to MgADP and metabolic inhibition, decreased sensitivity to glibenclamide, and responds to both diazoxide and pinacidil. Because this conservative amino acid substitution occurs in the SUR2A and SUR2B isoforms, the mutation provides a mechanism by which functional diversities in K ATP channels are generated.ATP-sensitive potassium (K ATP ) channels play a key role in linking metabolism to membrane excitability in muscle, neurons, and endocrine cells (1, 2). Each K ATP channel complex is composed of four subunits of a regulatory sulfonylurea receptor (SUR) 1 and four subunits of a pore-forming inward rectifier potassium channel Kir6.2 (3-5). The activity of K ATP channels is regulated by intracellular ATP and ADP; ATP inhibits channel activity via nonhydrolytic binding to the channel, whereas ADP stimulates channel activity in the presence of Mg 2ϩ in a nucleotide hydrolysis-dependent way (1, 2). Structure-function studies have led to the current view that the Kir6.2 subunit mediates channel inhibition by ATP (6, 7), and the SUR subunit mediates the stimulatory effects of MgADP as well as channel response to sulfonylureas and potassium channel openers (KCOs) (8 -12). There are two known SUR genes, SUR1 and SUR2. SUR2 further gives rise to several splice variants, the major ones being SUR2A and -2B, which differ in the last 42 amino acids. SUR1, SUR2A, and SUR2B, when combined with Kir6.2, form the pancreatic, cardiac, and vascular smooth muscle subtypes of K ATP channels, respectively (10, 13-16). These subtypes of K ATP channels differ in their sensitivities to nucleotides, sulfonylureas, and KCOs (8,17). SURs belong to the ATP Binding Cassette family of membrane proteins (ABC transporters); each SUR molecule contains two of the nucleotide binding domains (NBD) that are highly conserved in all ABC transporters. Biochemical evidence suggests that hydrolysis of MgATP at NBD2 stabilizes binding of ATP at NBD1 and thereby facilitates functional coupling between SUR1 and Kir6.2 and channel activation (18 -20). An increase in ADP concentrations stimulates channel activity...