scholarly journals Optogenetic modulation of cardiac action potential properties may prevent arrhythmogenesis in short and long QT syndromes

JCI Insight ◽  
2021 ◽  
Vol 6 (11) ◽  
Author(s):  
Amit Gruber ◽  
Oded Edri ◽  
Irit Huber ◽  
Gil Arbel ◽  
Amira Gepstein ◽  
...  
Keyword(s):  
Action Potential ◽  
Cardiac Action Potential ◽  
Long Qt ◽  
Cardiac Action

scholarly journals Stochastic pacing reveals the propensity to cardiac action potential alternans and uncovers its underlying dynamics

2016 ◽  
Vol 594 (9) ◽  
pp. 2537-2553 ◽  
Author(s):  
Yann Prudat ◽  
Roshni V. Madhvani ◽  
Marina Angelini ◽  
Nils P. Borgstom ◽  
Alan Garfinkel ◽  
...  
Keyword(s):  
Action Potential ◽  
Cardiac Action Potential ◽  
Cardiac Action

scholarly journals Dynamics of the late Na+ current during cardiac action potential and its contribution to afterdepolarizations

2013 ◽  
Vol 64 ◽  
pp. 59-68 ◽  
Author(s):  
Balazs Horvath ◽  
Tamas Banyasz ◽  
Zhong Jian ◽  
Bence Hegyi ◽  
Kornel Kistamas ◽  
...  
Keyword(s):  
Action Potential ◽  
Cardiac Action Potential ◽  
Na Current ◽  
Cardiac Action

scholarly journals Ceramide modulates HERG potassium channel gating by translocation into lipid rafts

2010 ◽  
Vol 299 (1) ◽  
pp. C74-C86 ◽  
Author(s):  
Sindura B. Ganapathi ◽  
Todd E. Fox ◽  
Mark Kester ◽  
Keith S. Elmslie
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Lipid Rafts ◽  
Negative Impact ◽  
Cardiac Action Potential ◽  
Cholesterol Depletion ◽  
Cardiac Action ◽  
Herg Channels ◽  
The Impact ◽  
Action Potential Repolarization

Human ether-à-go-go-related gene (HERG) potassium channels play an important role in cardiac action potential repolarization, and HERG dysfunction can cause cardiac arrhythmias. However, recent evidence suggests a role for HERG in the proliferation and progression of multiple types of cancers, making it an attractive target for cancer therapy. Ceramide is an important second messenger of the sphingolipid family, which due to its proapoptotic properties has shown promising results in animal models as an anticancer agent . Yet the acute effects of ceramide on HERG potassium channels are not known. In the present study we examined the effects of cell-permeable C6-ceramide on HERG potassium channels stably expressed in HEK-293 cells. C6-ceramide (10 μM) reversibly inhibited HERG channel current (IHERG) by 36 ± 5%. Kinetically, ceramide induced a significant hyperpolarizing shift in the current-voltage relationship (Δ V1/2 = −8 ± 0.5 mV) and increased the deactivation rate (43 ± 3% for τfast and 51 ± 3% for τslow). Mechanistically, ceramide recruited HERG channels within caveolin-enriched lipid rafts. Cholesterol depletion and repletion experiments and mathematical modeling studies confirmed that inhibition and gating effects are mediated by separate mechanisms. The ceramide-induced hyperpolarizing gating shift (raft mediated) could offset the impact of inhibition (raft independent) during cardiac action potential repolarization, so together they may nullify any negative impact on cardiac rhythm. Our results provide new insights into the effects of C6-ceramide on HERG channels and suggest that C6-ceramide can be a promising therapeutic for cancers that overexpress HERG.

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