scholarly journals Ionic membrane conductance during the time course of the cardiac action potential.

1977 ◽  
Vol 268 (3) ◽  
pp. 655-695 ◽  
Author(s):  
Y Goldman ◽  
M Morad
Author(s):  
Massimiliano Zaniboni ◽  
Francesca Cacciani

A compact three-dimensional representation of cardiac action potential (AP) properties in terms of current source is presented here. The experimental protocol used to obtain such representation is based on the measure of instantaneous current-voltage relationships during the course of the AP. The procedure, which combines current- and voltage-clamps on patch clamped cardiac myocytes, has been previously applied to real cells, and then extended to computer simulations with cellular ventricular AP models. The three-dimensional AP representation allows to easily estimate membrane resistance during repolarization, a key factor for the modulation of ventricular repolarization. It also shows that, during late ventricular repolarization, membrane conductance becomes negative, <em>i.e.</em> repolarization is auto-regenerative. The novel AP representation is therefore a useful tool for both in vivo and in silico cardiac cellular electrophysiological investigations.


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

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

2010 ◽  
Vol 299 (1) ◽  
pp. C74-C86 ◽  
Author(s):  
Sindura B. Ganapathi ◽  
Todd E. Fox ◽  
Mark Kester ◽  
Keith S. Elmslie

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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