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This suggests that the mitochondrial stress created by sustained Ca2+ entry could be responsible for their selective vulnerability, rather than simply a late stage consequence [41], [42].
LPA also evoked Ca2+ release in keratinocytes but failed to induce sustained Ca2+ entry even when extracellular Ca2+ was elevated to 1·2 mmol L−1.
To unravel a potential role for TRPM2 in sustained Ca2+ entry evoked by 8-Br N-cIDPR, TRPM2 was overexpressed in HEK (human embryonic kidney -293 cells.
The concentration-response analysis in respect of cytosolic Ca2+ elevation in response to LPI revealed the initial intracellular Ca2+ mobilization to be more sensitive than the sustained Ca2+ entry.
Our data with nifedipine shows that although it abolishes action potentials, it does not affect membrane potential and only a small part (about 25-35%) of the sustained Ca2+ entry via L-type Ca2+ channels.
In addition, the duration of the transient was not significantly altered by the inclusion of 10 mmol L−1 EGTA in the medium, indicating that sustained Ca2+ entry did not occur (data not shown).
By contrast, mutation of the diglycine motif and association with a peptide motif linked to the Tat or poly arginine PTD permits efficient entry and the mechanism sustaining this entry is energy-independent.
When anisotropy is removed, sustained re-entry cannot be initiated.
With ion channel remodelling only, sustained re-entry cannot be initiated.
With full remodelling, the same pacing protocol can generate sustained re-entry.
Both electrical heterogeneity and anisotropy contribute to the generation of conduction block and the propagation pattern promoting sustained re-entry.
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