Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells

2012 ◽  
Vol 386 (3) ◽  
pp. 239-246 ◽  
Author(s):  
László Szabó ◽  
Norbert Szentandrássy ◽  
Kornél Kistamás ◽  
Bence Hegyi ◽  
Ferenc Ruzsnavszky ◽  
...  
Keyword(s):  
Action Potential ◽  
Ion Currents ◽  
Ventricular Cells ◽  
Action Potential Configuration

scholarly journals Canine Myocytes Represent a Good Model for Human Ventricular Cells Regarding Their Electrophysiological Properties

2021 ◽  
Vol 14 (8) ◽  
pp. 748
Author(s):  
Péter P. Nánási ◽  
Balázs Horváth ◽  
Fábián Tar ◽  
János Almássy ◽  
Norbert Szentandrássy ◽  
...  
Keyword(s):  
Action Potential ◽  
Time Course ◽  
Laboratory Animals ◽  
Delayed Rectifier ◽  
Ion Currents ◽  
Human Cardiomyocytes ◽  
Ventricular Cells ◽  
Repolarization Reserve ◽  
Electrophysiological Studies ◽  
K Current

Due to the limited availability of healthy human ventricular tissues, the most suitable animal model has to be applied for electrophysiological and pharmacological studies. This can be best identified by studying the properties of ion currents shaping the action potential in the frequently used laboratory animals, such as dogs, rabbits, guinea pigs, or rats, and comparing them to those of human cardiomyocytes. The authors of this article with the experience of three decades of electrophysiological studies, performed in mammalian and human ventricular tissues and isolated cardiomyocytes, summarize their results obtained regarding the major canine and human cardiac ion currents. Accordingly, L-type Ca2+ current (ICa), late Na+ current (INa-late), rapid and slow components of the delayed rectifier K+ current (IKr and IKs, respectively), inward rectifier K+ current (IK1), transient outward K+ current (Ito1), and Na+/Ca2+ exchange current (INCX) were characterized and compared. Importantly, many of these measurements were performed using the action potential voltage clamp technique allowing for visualization of the actual current profiles flowing during the ventricular action potential. Densities and shapes of these ion currents, as well as the action potential configuration, were similar in human and canine ventricular cells, except for the density of IK1 and the recovery kinetics of Ito. IK1 displayed a largely four-fold larger density in canine than human myocytes, and Ito recovery from inactivation displayed a somewhat different time course in the two species. On the basis of these results, it is concluded that canine ventricular cells represent a reasonably good model for human myocytes for electrophysiological studies, however, it must be borne in mind that due to their stronger IK1, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.

Two types of action potential configuration in single cardiac Purkinje cells of sheep

1999 ◽  
Vol 277 (4) ◽  
pp. H1299-H1310 ◽  
Author(s):  
Arie O. Verkerk ◽  
Marieke W. Veldkamp ◽  
Fabio Abbate ◽  
Gudrun Antoons ◽  
Lennart N. Bouman ◽  
...  
Keyword(s):  
Action Potential ◽  
Purkinje Cells ◽  
Action Potentials ◽  
Phase 1 ◽  
Stimulus Frequency ◽  
Ventricular Cells ◽  
Cardiac Purkinje Cells ◽  
Current Densities ◽  
Lp Cells ◽  
Action Potential Configuration

Membrane potentials and currents of isolated sheep Purkinje and ventricular cells were compared using patch-clamp and microelectrode techniques. In ∼50% of Purkinje cells, we observed action potentials that showed a prominent phase 1 repolarization and relatively negative plateau (LP cells). Action potential configuration of the remaining Purkinje cells was characterized by little phase 1 repolarization and relatively positive plateau (HP cells). Microelectrode impalement of Purkinje strands also revealed these two types of action potential configuration. In LP cells, the density of L-type Ca2+ current ( I Ca,L) was lower, whereas the density of transient outward K+ current was higher, than in HP cells. Action potentials of HP cells strongly resembled those of ventricular cells. Densities of inward rectifier current and I Ca,L were significantly higher in ventricular cells compared with densities in both LP and HP Purkinje cells. Differences in current densities explain the striking differences in action potential configuration and the stimulus frequency dependency thereof that we observed in LP, HP, and ventricular cells. We conclude that LP Purkinje cells, HP Purkinje cells, and ventricular cells of sheep each have a unique action potential configuration.

scholarly journals Effects of Ropivacaine on Action Potential Configuration and Ion Currents in Isolated Canine Ventricular Cardiomyocytes

2008 ◽  
Vol 108 (4) ◽  
pp. 693-702 ◽  
Author(s):  
Adrienn Szabó ◽  
Norbert Szentandrássy ◽  
Péter Birinyi ◽  
Balázs Horváth ◽  
Gergely Szabó ◽  
...  
Keyword(s):  
Action Potential ◽  
Voltage Clamp ◽  
Action Potentials ◽  
Potassium Current ◽  
Maximum Velocity ◽  
Delayed Rectifier ◽  
Ion Currents ◽  
Ventricular Cardiomyocytes ◽  
Delayed Rectifier Potassium Current ◽  
Action Potential Configuration

Background Despite the widespread clinical application of ropivacaine, there is little information on the cellular cardiac effects of the drug. In the current study, therefore, the concentration-dependent effects of ropivacaine on action potential morphology and the underlying ion currents were studied and compared with those of bupivacaine in isolated canine ventricular cardiomyocytes. Methods Action potentials were recorded from the enzymatically dispersed cells using sharp microelectrodes. Conventional patch clamp and action potential voltage clamp arrangements were used to study the effects of ropivacaine on transmembrane ion currents. Results Ropivacaine induced concentration- and frequency-dependent changes in action potential configuration, including shortening of the action potentials, reduction of their amplitude and maximum velocity of depolarization, suppression of early repolarization, and depression of plateau. Reduction in maximum velocity of depolarization was characterized with an EC50 value of 81 +/- 7 microm at 1 Hz. Qualitatively similar results were obtained with bupivacaine (EC50 = 47 +/- 3 microm). Under voltage clamp conditions, a variety of ion currents were blocked by ropivacaine: L-type calcium current (EC50 = 263 +/- 67 microm), transient outward current (EC50 = 384 +/- 75 microm), inward rectifier potassium current (EC50 = 372 +/- 35 microm), rapid delayed rectifier potassium current (EC50 = 303 +/- 47 microm), and slow delayed rectifier potassium current (EC50 = 106 +/- 18 microm). Conclusions Ropivacaine, similarly to bupivacaine, can modify cardiac action potentials and the underlying ion currents at concentrations higher than the usual therapeutic range. However, in cases of overdose, cardiac complications may be anticipated both during and after anesthesia due to the blockade of various ion currents.

Basis for tetrodotoxin and lidocaine effects on action potentials in dog ventricular myocytes

1988 ◽  
Vol 254 (6) ◽  
pp. H1157-H1166 ◽  
Author(s):  
J. A. Wasserstrom ◽  
J. J. Salata
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Ionic Currents ◽  
Detectable Effect ◽  
Na Channel ◽  
Na Current ◽  
Voltage Range ◽  
Purkinje Fibers ◽  
Ventricular Cells

We studied the effects of tetrodotoxin (TTX) and lidocaine on transmembrane action potentials and ionic currents in dog isolated ventricular myocytes. TTX (0.1-1 x 10(-5) M) and lidocaine (0.5-2 x 10(-5) M) decreased action potential duration, but only TTX decreased the maximum rate of depolarization (Vmax). Both TTX (1-2 x 10(-5) M) and lidocaine (2-5 x 10(-5) M) blocked a slowly inactivating toward current in the plateau voltage range. The voltage- and time-dependent characteristics of this current are virtually identical to those described in Purkinje fibers for the slowly inactivating inward Na+ current. In addition, TTX abolished the outward shift in net current at plateau potentials caused by lidocaine alone. Lidocaine had no detectable effect on the slow inward Ca2+ current and the inward K+ current rectifier, Ia. Our results indicate that 1) there is a slowly inactivating inward Na+ current in ventricular cells similar in time, voltage, and TTX sensitivity to that described in Purkinje fibers; 2) both TTX and lidocaine shorten ventricular action potentials by reducing this slowly inactivating Na+ current; 3) lidocaine has no additional actions on other ionic currents that contribute to its ability to abbreviate ventricular action potentials; and 4) although both agents shorten the action potential by the same mechanism, only TTX reduces Vmax. This last point suggests that TTX produces tonic block of Na+ current, whereas lidocaine may produce state-dependent Na+ channel block, namely, blockade of Na+ current only after Na+ channels have already been opened (inactivated-state block).

Effects of ACh and adenosine mediated by Kir3.1 and Kir3.4 on ferret ventricular cells

2002 ◽  
Vol 283 (2) ◽  
pp. H615-H630 ◽  
Author(s):  
H. Dobrzynski ◽  
N. C. Janvier ◽  
R. Leach ◽  
J. B. C. Findlay ◽  
M. R. Boyett
Keyword(s):  
Action Potential ◽  
Outward Current ◽  
Current Clamp ◽  
Inotropic Effects ◽  
Clamp Technique ◽  
Action Potential Clamp ◽  
Ventricular Cells ◽  
Action Potential Waveform ◽  
Potential Waveform ◽  
Action Potential Shortening

The inotropic effects of ACh and adenosine on ferret ventricular cells were investigated with the action potential-clamp technique. Under current clamp, both agonists resulted in action potential shortening and a decrease in contraction. Under action potential clamp, both agonists failed to decrease contraction substantially. In the absence of agonist, application of the short action potential waveform (recorded previously in the presence of agonist) also resulted in a decrease in contraction. Under action potential clamp, application of ACh resulted in a Ba2+-sensitive outward current with the characteristics of muscarinic K+ current ( I K,ACh); the presence of the muscarinic K+ channel was confirmed by PCR and immunocytochemistry. In the absence of agonist, on application of the short ACh action potential waveform, the decrease in contraction was accompanied by loss of the inward Na+/Ca2+exchange current ( I NaCa). ACh also inhibited the background inward K+ current ( I K,1). It is concluded that ACh activates I K,ACh, inhibits I K,1, and indirectly inhibits I NaCa; this results in action potential shortening, decrease in contraction, and, as a result of the inhibition of I K,1, minimum decrease in excitability.

Determinants of action potential initiation in isolated rabbit atrial and ventricular myocytes

1998 ◽  
Vol 274 (6) ◽  
pp. H1902-H1913 ◽  
Author(s):  
David A. Golod ◽  
Rajiv Kumar ◽  
Ronald W. Joyner
Keyword(s):  
Action Potential ◽  
Ventricular Myocytes ◽  
Cell Types ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Isolated Cells ◽  
Atrial Cells ◽  
Ventricular Cells ◽  
Action Potential Initiation ◽  
Potential Initiation

Action potential conduction through the atrium and the ventricle of the heart depends on the membrane properties of the atrial and ventricular cells, particularly with respect to the determinants of the initiation of action potentials in each cell type. We have utilized both current- and voltage-clamp techniques on isolated cells to examine biophysical properties of the two cell types at physiological temperature. The resting membrane potential, action potential amplitude, current threshold, voltage threshold, and maximum rate of rise measured from atrial cells (−80 ± 1 mV, 109 ± 3 mV, 0.69 ± 0.05 nA, −59 ± 1 mV, and 206 ± 17 V/s, respectively; means ± SE) differed significantly ( P < 0.05) from those values measured from ventricular cells (−82.7 ± 0.4 mV, 127 ± 1 mV, 2.45 ± 0.13 nA, −46 ± 2 mV, and 395 ± 21 V/s, respectively). Input impedance, capacitance, time constant, and critical depolarization for activation also were significantly different between atrial (341 ± 41 MΩ, 70 ± 4 pF, 23.8 ± 2.3 ms, and 19 ± 1 mV, respectively) and ventricular (16.5 ± 5.4 MΩ, 99 ± 4.3 pF, 1.56 ± 0.32 ms, and 36 ± 1 mV, respectively) cells. The major mechanism of these differences is the much greater magnitude of the inward rectifying potassium current in ventricular cells compared with that in atrial cells, with an additional difference of an apparently lower availability of inward Na current in atrial cells. These differences in the two cell types may be important in allowing the atrial cells to be driven successfully by normal regions of automaticity (e.g., the sinoatrial node), whereas ventricular cells would suppress action potential initiation from a region of automaticity (e.g., an ectopic focus).

Cytosolic magnesium modulates calcium channel activity in mammalian ventricular cells

1989 ◽  
Vol 256 (2) ◽  
pp. C452-C455 ◽  
Author(s):  
Z. S. Agus ◽  
E. Kelepouris ◽  
I. Dukes ◽  
M. Morad
Keyword(s):  
Action Potential ◽  
Calcium Channel ◽  
Action Potential Duration ◽  
Calcium Current ◽  
Concentration Addition ◽  
High Threshold ◽  
Channel Activity ◽  
Mean Values ◽  
Ventricular Cells ◽  
In Cells

The effect of cytosolic free Mg2+ concentration on the regulation of myocardial function was studied by dialyzing isolated guinea pig ventricular myocytes with different internal Mg2+ concentrations [( Mg2+]i). We found that elevation of [Mg2+]i shortened the action potential and suppressed the Ca2+ current. Mean values recorded for action potential duration in cells dialyzed with solutions containing 0, 1.3, and 9.4 mM Mg2+ were 620 +/- 40, 400 +/- 25, and 60 +/- 10, respectively. The suppressive effect of [Mg2+]i on the action potential duration correlated significantly with the suppressive effects of [Mg2+]i on the Ca2+ current. In cells dialyzed with nominally zero Mg2+, calcium current was prominent (3.5 +/- 0.58 nA). At [Mg2+]i of 1.4 mM, calcium current was significantly smaller than in zero [Mg2+]i and was almost completely inhibited by dialysis of the cell with 9.4 mM Mg2+. The Mg2+-induced block of the Ca2+ current was due to steady-state inactivation of the high threshold calcium channel. The block was observed in the presence or absence of adenosine 3',5'-cylic monophosphate and was not reversed by elevation of external Ca2+ concentration, addition of adrenaline, or large negative potentials. These data suggest that cytosolic Mg2+ regulates Ca2+ channel activity by a novel mechanism, unrelated to its effect as a blocking particle of the open channel.

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