Late scattered openings (LSM) gating was significantly slower in failing compared to normal myocytes (tau=474±10 vs. 299±9 ms; P<0.05), demonstrating a multi-modal composition of late Na+ current.
The late Na+ current decay is composed of three gating modes, with late scattered openings being significantly slower in failing human ventricular cardiomyocytes, providing a rationale for INaL modulation.
Absolute Event Rate: 474% vs 299%
p-value: p=<0.05
OBJECTIVE: We reported an ultraslow late Na+ current (INaL) in ventricular cardiomyocytes of human hearts. INaL has been implicated in regulation of action potential duration in normal hearts and repolarization abnormalities in failing hearts. We have also identified sodium channel (NaCh) gating modes including bursts (BM) and late scattered openings (LSM) that together comprise INaL; however, the contribution of these gating modes to Na+ current (INa) remains unknown. In the present study, the late NaCh activity was recorded, analyzed, and modeled for heterologously expressed NaCh, Nav1.5, and for the native NaCh of ventricular mid-myocardial cardiomyocytes from normal and failing hearts. METHODS AND RESULTS: We found that LSM gating was significantly slower in failing compared to normal myocytes and Nav1.5 (tau=474+/-10 vs. 299+/-9, and 229+/-12 ms, m+/-SEM; P300 ms) is determined solely by LSM. The concept of multi-mode composition for INaL provides a new rationale for INaL modulation by factors such as voltage, temperature, pharmacological agents, and pathological conditions.
Maltsev et al. (Wed,) conducted a other in Heart failure. Late scattered openings (LSM) gating was significantly slower in failing compared to normal myocytes (tau=474±10 vs. 299±9 ms; P<0.05), demonstrating a multi-modal composition of late Na+ current.
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