Syntaxin-1A modulation of ATP-sensitive potassium channels: Implications on cardiac pathophysiology and beta-cell therapeutics.
Published: 2006
Language: eng
Number of pages: 122
ISBN-13: 9780494213773
Description: The current study examines the physiological importance of Syntaxin-1A (Syn-1A) regulation of ATP-sensitive potassium (KATP) channels. We found that Syn-1A reversed the effects of proton activation in cardiac KATP channels, exerted through an enhanced physical interaction between Syn-1A and the nucleotide binding folds (NBFs) of the channel in acidosis. As pH decreases prominently during early cardiac stress, Syn-1A may act as a physiological brake to limit K+ efflux and thus reduce the risk of arrhythmogenesis in these situations. In pancreatic beta-cells, cytoplasmic Syn-1A reduced the potency and efficacy of novel beta-cell-selective KATP channel opener (KCO) NNC 55-0462. The reduction of Syn-1A expression in diabetes may enhance the effectiveness of KCO therapy by increasing its efficacy and specificity. The ability of Syn-1A to modulate both cardiac and beta-cell KATP channels under different stimulus suggests that it regulates a common mechanistic pathway, possibly via interference with adenosine nucleotide activation on the NBFs.
Notes: Source: Masters Abstracts International, Volume: 45-03, page: 1354.

Thesis (M.Sc.)--University of Toronto, 2006.

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