scholarly journals Size and Ionic Currents of Unexcitable Cells Coupled to Cardiomyocytes Distinctly Modulate Cardiac Action Potential Shape and Pacemaking Activity in Micropatterned Cell Pairs

2012 ◽  
Vol 5 (4) ◽  
pp. 821-830 ◽  
Author(s):  
Luke C. McSpadden ◽  
Hung Nguyen ◽  
Nenad Bursac
Keyword(s):  
Action Potential ◽  
Ionic Currents ◽  
Cardiac Action Potential ◽  
Cardiac Action ◽  
Potential Shape ◽  
Action Potential Shape

Biphasic Effects of Isoflurane on the Cardiac Action Potential

2002 ◽  
Vol 97 (5) ◽  
pp. 1209-1217 ◽  
Author(s):  
Akihiro Suzuki ◽  
Kei Aizawa ◽  
Susanne Gassmayr ◽  
Zeljko J. Bosnjak ◽  
Wai-Meng Kwok
Keyword(s):  
Action Potential ◽  
Cardiac Electrophysiology ◽  
Ionic Currents ◽  
Cardiac Action Potential ◽  
Delayed Rectifier ◽  
Inactivation Kinetics ◽  
Inhibitory Effects ◽  
Patch Clamp Technique ◽  
Cardiac Action ◽  
Chord Conductance

Background The mechanism underlying isoflurane modulation of cardiac electrophysiology is not well understood. In the present study, the authors investigated the effects of isoflurane on the cardiac action potential (AP) characteristics. The results were correlated to modulation of the L-type calcium (I(Ca,L)), the delayed-rectifier potassium (I(Kdr)), and the inward-rectifier potassium (I(Kir)) currents. Methods Single ventricular myocytes were enzymatically isolated from guinea pig hearts. The current clamp and whole cell voltage clamp configurations of the patch clamp technique were used to monitor the cardiac AP and ionic currents, respectively. A dynamic AP voltage protocol that mimicked changes in membrane potential during an AP was used to monitor the I(Ca,L), I(Kdr) and I(Kir). Results Isoflurane produced a concentration-dependent, biphasic effect on the AP duration (APD). At 0.6 mm (1.26 vol%), isoflurane significantly increased APD50 and APD90 by 50.0 +/- 7.6% and 48.9 +/- 7.2%, respectively (P < 0.05; n = 6). At 1.0 mm (2.09 vol%), isoflurane had no significant effect on APD (n = 6). In contrast, at 1.8 mm (3.77 vol%), isoflurane decreased APD50 and APD90 by 38.3 +/- 5.4% and 32.2 +/- 5.5%, respectively (P < 0.05; n = 7). The inhibitory effects of isoflurane on I(Kdr) chord conductance were greater than those on I(Ca,L) (P < 0.05; n = 6/group). Both I(Ca,L) inactivation and I(Kdr) activation kinetics were accelerated by isoflurane. Isoflurane had no significant effects on I(Kir) chord conductance (n = 6). Conclusion At the lower anesthetic concentration, the prolongation of the APD may be the result of the dominant inhibitory effects of isoflurane on I(Kdr). At the higher concentration, the shortening of the APD may be caused by the inhibitory effects on I (Ca,L) combined with the isoflurane-induced acceleration of I(Ca,L) inactivation kinetics. Because I(Kdr) is significantly inhibited by isoflurane, I(Kir) appears to be the major repolarizing current, which is minimally affected by isoflurane.

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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