No abstract

No abstract

SCN5A is expressed in cardiomyocytes and gastrointestinal (GI) smooth muscle cells (SMCs) as the voltage-gated mechanosensitive sodium channel Na V 1.5. The influx of Na + through Na V 1.5 produces a fast depolarization in membrane potential, indispensable for electrical excitability in cardiomyocytes and important for electrical slow waves in GI smooth muscle. As such, abnormal Na V 1.5 voltage gating or mechanosensitivity may result in channelopathies. SCN5A mutation G615Efound separately in cases of acquired long-QT syndrome, sudden cardiac death, and irritable bowel syndromehas a relatively minor effect on Na V 1.5 voltage gating. The aim of this study was to test whether G615E impacts mechanosensitivity. Mechanosensitivity of wild-type (WT) or G615E-Na V 1.5 in HEK-293 cells was examined by shear stress on voltage-or current-clamped whole cells or pressure on macroscopic patches. Unlike WT, voltage-clamped G615E-Na V 1.5 showed a loss in shear-and pressure-sensitivity of peak current yet a normal leftward shift in the voltage-dependence of activation. In current-clamp, shear stress led to a significant increase in firing spike frequency with a decrease in firing threshold for WT but not G615E-Na V 1.5. Our results show that the G615E mutation leads to functionally abnormal Na V 1.5 channels, which cause disruptions in mechanosensitivity and mechano-electrical feedback and suggest a potential contribution to smooth muscle pathophysiology.

Background Facial aging is a multi-factorial process which involves all tissues of the face including skin, muscles, fat, ligaments, and bone. Whereas robust evidence is available for age-related changes of bone and facial fat, the influence of age on facial muscle activity is poorly understood. Objectives The objective of this study was to investigate the motor unit action potential (MUAP) of facial muscles by utilizing surface derived, non-invasive electromyography in young and old healthy volunteers. Methods The study investigated a total of 32 healthy volunteers with a mean age of 42.6 (19.6) years [range: 21 – 82] and a mean body mass index (BMI) of 23.9 (2.7) kg/m 2 [range: 18.5 – 29.7] utilizing surface derived, non-invasive facial electromyography. A total of 9 facial muscles were investigated bilaterally resulting in a total of 1632 measurements of the signal, baseline noise and signal-to-noise ratio of the nine muscles. Results The results of the study revealed that age does not significantly influence the signal (p = 0.234), the baseline noise (p = 0.225) or the signal-to-noise ratio (SNR; p = 0.432) when younger individuals (< 30 years) were compared to older individuals (> 50 years) in a gender and BMI matched statistical model. Exceptions were the (reduced muscle activity), procerus (increased activity), and corrugator supercilii (increased activity) muscles. Conclusions The results of this facial EMG study may help to increase the understanding of facial aging. Future studies need to reproduce the results presented herein to further increase our understanding of facial aging.

No abstract