Variability in timing of spontaneous calcium release in the intact rat heart is determined by the time course of sarcoplasmic reticulum calcium load.

BACKGROUND: Abnormalities in intracellular calcium (Ca) cycling during Ca overload can cause triggered activity because spontaneous calcium release (SCR) activates sufficient Ca-sensitive inward currents to induce delayed afterdepolarizations (DADs). However, little is known about the mechanisms relating SCR and triggered activity on the tissue scale. METHODS AND RESULTS: Laser scanning confocal microscopy was used to measure the spatiotemporal properties of SCR within large myocyte populations in intact rat heart. Computer simulations were used to predict how these properties of SCR determine DAD magnitude. We measured the average and standard deviation of the latency distribution of SCR within a large population of myocytes in intact tissue. We found that as external [Ca] is increased, and with faster pacing rates, the average and SD of the latency distribution decreases substantially. This result demonstrates that the timing of SCR occurs with less variability as the sarcoplasmic reticulum (SR) Ca load is increased, causing more sites to release Ca within each cell. We then applied a mathematical model of subcellular Ca cycling to show that a decrease in SCR variability leads to a higher DAD amplitude and is dictated by the rate of SR Ca refilling following an action potential. CONCLUSIONS: Our results demonstrate that the variability of the timing of SCR in a population of cells in tissue decreases with SR load and is dictated by the time course of the SR Ca content.

Female Caregivers' Depression Risk Affects Children's Attendance to Dental Appointments: A Pilot Study.

Purpose: This pilot study aimed to evaluate the association between women's depression risk and their children's return for dental treatment. Methods: A total of 175 female caregivers of children presenting for an initial dental examination between May and October 2019 at a university clinic answered demographic questions and a validated survey on depression risk. An analysis of caregiver's depression risk relative to children's attendance at the next treatment appointment was made. Results: One hundred and eight female caregivers were included in the analysis. Average age was 33 years (standard deviation ± 6.5 years), and 52 percent were Hispanic. The rate of risk for depression was 17.5 percent. Most women at risk lived at least 20 miles away, had an income of less than $29,999, were unemployed or employed part-time, and had no help with childcare. White caregivers were more likely to fail to attend their child's appointment (chi-square [X²] = 7.80, P=0.02) while Hispanic women were more likely to return (X² = 4.10, P=0.04). Caregivers with low depression risk were more likely to return for the child's scheduled appointment (X² = 13.37, P<0.001). Thus, there was a positive association between high depression risk and failed appointments (r=0.474, P<0.01). Conclusion: Children of women at risk for depression are more likely to fail to attend their dental appointment.

Characteristics of intracellular Ca2+ cycling in intact rat heart: a comparison of sex differences.

Males and females show distinct differences in action potential waveform, ion channel expression patterns, and ECG characteristics. However, it is not known how sex-based differences in Ca2+ cycling might contribute to these differences in electrophysiological activity. The goal of this study was to investigate the differences in cellular Ca2+ transients in males and females and to examine how these might contribute to electrophysiological function. Ca2+ transients were measured in individual myocytes within microscopic regions of the fluo-4 AM-loaded left ventricular epicardium of intact rat heart of both sexes (3 to 5 mo old). Pacing protocols were used to measure transient characteristics at a basic cycle length of 500 ms and during 10-s trains of rapid pacing delivered to the left ventricular apex. Ca2+ transients were smaller in magnitude and longer in duration in females than in males. More importantly, the variability in Ca2+ transient characteristics between myocytes in a microscopic recording site (heterogeneity index) was greater for females than males for characteristics related to transient duration. The rate sensitivity of Ca2+ alternans development in individual myocytes was greater in females than in males, but there was also a greater heterogeneity in cellular responses to the rate dependence of alternans development in females. The longer Ca2+ transients in females were also associated with slower restitution, which was likely to be responsible for the development of Ca2+ and repolarization alternans at slower heart rates. These results demonstrate that there are distinct differences in cellular Ca2+ cycling in male and female rat hearts. Not only is there slower reuptake of Ca2+ in female rats, but there is greater local variability in Ca2+ cycling at the microscopic level. These sex-based differences in Ca2+ cycling could contribute to differences in ECG morphology and in arrhythmia sensitivity in males and females.