Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes.

The four hyperpolarization-activated cylic-nucleotide gated (HCN) channel isoforms and their auxiliary subunit KCNE2 are important in the regulation of peripheral and central neuronal firing and the heartbeat. Disruption of their normal function has been implicated in cardiac arrhythmias, peripheral pain, and epilepsy. However, molecular details of the HCN-KCNE2 complexes are unknown. Using single-molecule subunit counting, we determined that the number of KCNE2 subunits in complex with the pore-forming subunits of human HCN channels differs with each HCN isoform and is dynamic with respect to concentration. These interactions can be altered by KCNE2 gene-variants with functional implications. The results provide an additional consideration necessary to understand heart rhythm, pain, and epileptic disorders.

Immigration factors and potentially avoidable hospitalizations in Canada.

OBJECTIVE: Estimate the effect of immigration characteristics on the risk of a hospitalization for an ambulatory care sensitive condition (ACSC). RESEARCH DESIGN: We analyzed data on the Canadian resident adult population aged 18 to 74 years who responded to the 2006 long form Census. The Census data were linked to the Canadian Institute for Health Information (CIHI)'s Discharge Abstract Database (DAD) for fiscal years 2006-2007, 2007-2008, and 2008-2009. We conducted a logistic regression on the binary variable we created for an ACSC admission. MEASURES: The CIHI definition of ACSC hospitalizations was used to identify potentially avoidable hospitalizations in the DAD. Immigration factors analyzed included years in Canada, ethnic origin, and ability to speak one of the official languages. RESULTS: There were 3,342,450 respondents aged between 18 and 74. Using the Canadian at birth as our reference population, recent immigrants (up to five years in Canada) had lower odds of an ACSC hospitalization, regardless of their ethnic origins, with the exception of immigrants from Oceania and from other North American countries for whom the effect was not significant. The protective effect was still present in children of immigrants (AOR=0.89). Immigrants from the Caribbean, from Southern, Eastern, and Western Europe, as well as those from East Asia had lower odds across categories of time spent in Canada. The protective effect was stronger in immigrants from East Asia and lower in those of Oceanic and other North American countries. CONCLUSIONS: Our results suggest that the healthy immigrant effect dissipates with time in Canada but remains even in children of immigrants. The protective effect differs depending on the ethnic origin of the immigrant.