KCNH2 encodes a nuclear-targeted polypeptide that mediates hERG1 channel gating and expression.

KCNH2 encodes hERG1, the voltage-gated potassium channel that conducts the rapid delayed rectifier potassium current (IKr) in human cardiac tissue. hERG1 is one of the first channels expressed during early cardiac development, and its dysfunction is associated with intrauterine fetal death, sudden infant death syndrome, cardiac arrhythmia, and sudden cardiac death. Here, we identified a hERG1 polypeptide (hERG1NP) that is targeted to the nuclei of immature cardiac cells, including human stem cell-derived cardiomyocytes (hiPSC-CMs) and neonatal rat cardiomyocytes. The nuclear hERG1NP immunofluorescent signal is diminished in matured hiPSC-CMs and absent from adult rat cardiomyocytes. Antibodies targeting distinct hERG1 channel epitopes demonstrated that the hERG1NP signal maps to the hERG1 distal C-terminal domain. KCNH2 deletion using CRISPR simultaneously abolished IKr and the hERG1NP signal in hiPSC-CMs. We then identified a putative nuclear localization sequence (NLS) within the distal hERG1 C-terminus, 883-RQRKRKLSFR-892. Interestingly, the distal C-terminal domain was targeted almost exclusively to the nuclei when overexpressed HEK293 cells. Conversely, deleting the NLS from the distal peptide abolished nuclear targeting. Similarly, blocking α or ß1 karyopherin activity diminished nuclear targeting. Finally, overexpressing the putative hERG1NP peptide in the nuclei of HEK cells significantly reduced hERG1a current density, compared to cells expressing the NLS-deficient hERG1NP or GFP. These data identify a developmentally regulated polypeptide encoded by KCNH2, hERG1NP, whose presence in the nucleus indirectly modulates hERG1 current magnitude and kinetics.

'I feel like this will never end': mental health during the COVID-19 pandemic among older adults with chronic conditions.

OBJECTIVES: The COVID-19 pandemic may have a negative impact on mental health, especially among older adults with chronic conditions who are more vulnerable to severe illness. In this qualitative study, we evaluated how the pandemic has impacted the ways that adults aged 50 and older with chronic conditions managed their mental health. METHODS: A total of 492 adults (M = 64.95 years, SD = 8.91, range = 50-94) who lived in Michigan (82.1%) and 33 other U.S. states completed one anonymous online survey between 14 May 14 and 9 July 2020. Open-ended responses were coded to ascertain relevant concepts and were reduced to develop major themes. RESULTS: We determined four main themes. The COVID-19 pandemic impacted how participants took care of their mental health through: (1) pandemic-related barriers to social interaction; (2) pandemic-related routine changes; (3) pandemic-related stress; and (4) pandemic-related changes to mental health service use. CONCLUSION: This study indicates that older adults with chronic conditions experienced various challenges to managing their mental health in the early months of the COVID-19 pandemic, but also showed considerable resilience. The findings identify potential targets of personalized interventions to preserve their well-being during this pandemic and in future public health crises.

Loneliness During the COVID-19 Pandemic Among Older Adults With Chronic Conditions.

The COVID-19 pandemic may intensify loneliness among older adults with chronic conditions who are at high risk of severe illness, but little is known about factors associated with loneliness during the pandemic. We considered factors linked to loneliness among 701 adults aged 50 years and older with chronic conditions from Michigan (82.5%) and 33 other U.S. states. Participants completed an anonymous online survey between May 14 and July 9, 2020. About two thirds (66.4%) reported moderate to severe loneliness. The fully adjusted regression model revealed that being a person of color, having a spouse or cohabiting partner, and more emotional support were associated with lower levels of loneliness. Higher anxiety symptoms, more worry about COVID-19 infection, and more financial strain because of the pandemic were linked to greater loneliness. These findings inform strategies to support a vulnerable subgroup of older adults during this pandemic and in future public health crises.

Daily Social Interactions and HPA Axis Activity Among Midlife and Older Adults.

BACKGROUND AND OBJECTIVES: Older people experience fewer negative interactions and report less stress in response to interpersonal tensions. Less is known, however, about the implications of daily social interactions for biological stress responses. We evaluated links between daily positive and negative interactions and 2 key biomeasures of the hypothalamic-pituitary-adrenal axis: salivary cortisol and dehydroepiandrosterone sulfate (DHEA-S). We also considered the moderating effects of age. RESEARCH DESIGN AND METHODS: Participants included a random sample of 93 individuals aged 40-95 who completed 14 days of daily diary interviews and provided saliva samples during 4 of those days. RESULTS: Three-level piecewise models showed that individuals had higher sustained DHEA-S levels on days after reporting more positive interactions. Young-old adults (60-79) had lower overall DHEA-S on days when they had more negative interactions than oldest-old adults (80 and older). Oldest-old adults showed a flatter decline in DHEA-S on days after they reported more negative interactions compared to midlife adults (40-59). Daily social interactions were not significantly associated with cortisol. DISCUSSION AND IMPLICATIONS: Strategies to increase positive interactions may help to build physiological resilience to stress, particularly among midlife and young-old adults.