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 Bond graph modelling of the cardiac action potential: implications for drift and non-unique steady states

2018 ◽  
Vol 474 (2214) ◽  
pp. 20180106 ◽  
Author(s):  
Michael Pan ◽  
Peter J. Gawthrop ◽  
Kenneth Tran ◽  
Joseph Cursons ◽  
Edmund J. Crampin
Keyword(s):  
Action Potential ◽  
Conservation Laws ◽  
Cardiac Electrophysiology ◽  
Bond Graph ◽  
Steady States ◽  
Cardiac Action Potential ◽  
Bond Graphs ◽  
Charge Conservation ◽  
Cardiac Action ◽  
Wide Range

Mathematical models of cardiac action potentials have become increasingly important in the study of heart disease and pharmacology, but concerns linger over their robustness during long periods of simulation, in particular due to issues such as model drift and non-unique steady states. Previous studies have linked these to violation of conservation laws, but only explored those issues with respect to charge conservation in specific models. Here, we propose a general and systematic method of identifying conservation laws hidden in models of cardiac electrophysiology by using bond graphs, and develop a bond graph model of the cardiac action potential to study long-term behaviour. Bond graphs provide an explicit energy-based framework for modelling physical systems, which makes them well suited for examining conservation within electrophysiological models. We find that the charge conservation laws derived in previous studies are examples of the more general concept of a ‘conserved moiety’. Conserved moieties explain model drift and non-unique steady states, generalizing the results from previous studies. The bond graph approach provides a rigorous method to check for drift and non-unique steady states in a wide range of cardiac action potential models, and can be extended to examine behaviours of other excitable systems.

Discrepant effects of heart failure on electrophysiological property in right ventricular outflow tract and left ventricular outflow tract cardiomyocytes

2017 ◽  
Vol 131 (12) ◽  
pp. 1317-1327 ◽  
Author(s):  
Yen-Yu Lu ◽  
Chen-Chuan Cheng ◽  
Chin-Feng Tsai ◽  
Yung-Kuo Lin ◽  
Ting-I Lee ◽  
...  
Keyword(s):  
Heart Failure ◽  
Action Potential ◽  
Ventricular Arrhythmias ◽  
Ionic Currents ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Outflow Tract ◽  
Delayed Rectifier ◽  
Patch Clamp Technique ◽  
Left Ventricular Outflow

Ventricular arrhythmias commonly arise from the right (RVOT) and left ventricular outflow tracts (LVOT) in patients without structural heart disease. Heart failure (HF) significantly increases the risk of ventricular arrhythmias. The regional differences and how HF affects the electrophysiological characteristics of RVOT and LVOT cardiomyocytes remain unclear. The whole-cell patch-clamp technique was used to investigate the action potentials and ionic currents in isolated single RVOT and LVOT cardiomyocytes from control rabbits and rabbits with HF induced by rapid ventricular pacing. Comparison with control LVOT cardiomyocytes showed that control RVOT cardiomyocytes have a shorter action potential duration (APD), smaller late Na+ currents (INa-late), larger transient outward (Ito) and larger delayed rectifier K+ currents (IKr-tail), but had similar L-type Ca2+ currents (ICa-L) and Na+/Ca2+ exchanger (NCX) current. HF increased APD, INa-late and NCX, but decreased ICa-L and Ito in RVOT cardiomyocytes. In contrast with this, HF decreased APD and ICa-L, but increased Ito and IKr-tail in LVOT cardiomyocytes. In conclusion, RVOT and LVOT cardiomyocytes had distinctive electrophysiological characteristics. HF differentially modulates action potential morphology and ionic currents in RVOT and LVOT cardiomyocytes.

Thermal adaptation of the crucian carp (Carassius carassius) cardiac delayed rectifier current, IKs, by homomeric assembly of Kv7.1 subunits without MinK

2011 ◽  
Vol 301 (1) ◽  
pp. R255-R265 ◽  
Author(s):  
Minna Hassinen ◽  
Salla Laulaja ◽  
Vesa Paajanen ◽  
Jaakko Haverinen ◽  
Matti Vornanen
Keyword(s):  
Action Potential ◽  
Crucian Carp ◽  
Thermal Adaptation ◽  
Cardiac Action Potential ◽  
Delayed Rectifier ◽  
Carassius Carassius ◽  
Electrical Stability ◽  
Activation Kinetics ◽  
Cardiac Action ◽  
Wide Range

Ectothermic vertebrates experience acute and chronic temperature changes which affect cardiac excitability and may threaten electrical stability of the heart. Nevertheless, ectothermic hearts function over wide range of temperatures without cardiac arrhythmias, probably due to special molecular adaptations. We examine function and molecular basis of the slow delayed rectifier K+ current ( IKs) in cardiac myocytes of a eurythermic fish ( Carassius carassius L.). IKs is an important repolarizing current that prevents excessive prolongation of cardiac action potential, but it is extremely slowly activating when expressed in typical molecular composition of the endothermic animals. Comparison of the IKs of the crucian carp atrial myocytes with the currents produced by homomeric Kv7.1 and heteromeric Kv7.1/MinK channels in Chinese hamster ovary cells indicates that activation kinetics and pharmacological properties of the IKs are similar to those of the homomeric Kv7.1 channels. Consistently with electrophysiological properties and homomeric Kv7.1 channel composition, atrial transcript expression of the MinK subunit is only 1.6–1.9% of the expression level of the Kv7.1 subunit. Since activation kinetics of the homomeric Kv7.1 channels is much faster than activation of the heteromeric Kv7.1/MinK channels, the homomeric Kv7.1 composition of the crucian carp cardiac IKs is thermally adaptive: the slow delayed rectifier channels can open despite low body temperatures and curtail the duration of cardiac action potential in ectothermic crucian carp. We suggest that the homomeric Kv7.1 channel assembly is an evolutionary thermal adaptation of ectothermic hearts and the heteromeric Kv7.1/MinK channels evolved later to adapt IKs to high body temperature of endotherms.

scholarly journals Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current

2021 ◽  
Vol 22 (16) ◽  
pp. 8744
Author(s):  
Asfree Gwanyanya ◽  
Inga Andriulė ◽  
Bogdan M. Istrate ◽  
Farjana Easmin ◽  
Kanigula Mubagwa ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Action Potential ◽  
Voltage Clamp ◽  
Divalent Cation ◽  
Cardiac Myocyte ◽  
Cardiac Action Potential ◽  
Delayed Rectifier ◽  
Delayed Rectifier Current ◽  
Cardiac Action ◽  
In Cells

The cardiac Mg2+-sensitive, TRPM6, and TRPM7-like channels remain undefined, especially with the uncertainty regarding TRPM6 expression in cardiomyocytes. Additionally, their contribution to the cardiac action potential (AP) profile is unclear. Immunofluorescence assays showed the expression of the TRPM6 and TRPM7 proteins in isolated pig atrial and ventricular cardiomyocytes, of which the expression was modulated by incubation in extracellular divalent cation-free conditions. In patch clamp studies of cells dialyzed with solutions containing zero intracellular Mg2+ concentration ([Mg2+]i) to activate the Mg2+-sensitive channels, raising extracellular [Mg2+] ([Mg2+]o) from the 0.9-mM baseline to 7.2 mM prolonged the AP duration (APD). In contrast, no such effect was observed in cells dialyzed with physiological [Mg2+]i. Under voltage clamp, in cells dialyzed with zero [Mg2+]i, depolarizing ramps induced an outward-rectifying current, which was suppressed by raising [Mg2+]o and was absent in cells dialyzed with physiological [Mg2+]i. In cells dialyzed with physiological [Mg2+]i, raising [Mg2+]o decreased the L-type Ca2+ current and the total delayed-rectifier current but had no effect on the APD. These results suggest a co-expression of the TRPM6 and TRPM7 proteins in cardiomyocytes, which are therefore the molecular candidates for the native cardiac Mg2+-sensitive channels, and also suggest that the cardiac Mg2+-sensitive current shortens the APD, with potential implications in arrhythmogenesis.

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