scholarly journals Calmodulin kinase is functionally targeted to the action potential plateau for regulation of L-type Ca2+current in rabbit cardiomyocytes

2003 ◽  
Vol 554 (1) ◽  
pp. 145-155 ◽  
Author(s):  
Yuejin Wu ◽  
John T. Kimbrough ◽  
Roger J. Colbran ◽  
Mark E. Anderson
Keyword(s):  
Action Potential ◽  
Calmodulin Kinase ◽  
Action Potential Plateau ◽  
Potential Plateau

Transmembrane potential and force of contraction of the normal and potassium-deficient human atrial tissue in vitro

1969 ◽  
Vol 47 (12) ◽  
pp. 1015-1024 ◽  
Author(s):  
Kailash Prasad
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Terminal Phase ◽  
Free Solution ◽  
Force Of Contraction ◽  
Pacemaker Cells ◽  
Atrial Tissue ◽  
Action Potential Plateau ◽  
Potential Plateau

The characteristics of the simultaneously recorded action potential (AP) and contraction of isolated atrial tissue of human heart were studied in normal and in potassium-free solutions. Two types of action potentials associated with characteristic contractions were observed. Pacemaker types of action potentials with two humps in the plateau were observed in spontaneously beating atria and they were associated with triple contractions. A non-pacemaker type of action potential was found in quiescent fibers when the preparation was driven electrically; this resulted in single peak contraction. The sizes of the resting and action potentials of pacemaker cells were lower, while those of action potential duration in all types of cells were higher than those reported in other mammals. When spontaneously beating atrial pieces were exposed to a potassium-free solution there was a shortening of the action potential plateau and lengthening of the terminal phase of repolarization associated with the development of the first hump into a slow spike. The shortening of the action potential plateau associated with an increase in the force of contraction was also observed in electrically stimulated muscles in KCl-free solution.

Valinomycin shortening of action potential of embryonic chick hearts

1975 ◽  
Vol 228 (4) ◽  
pp. 1113-1117 ◽  
Author(s):  
K Shigenobu ◽  
N Sperelakis
Keyword(s):  
Action Potential ◽  
Threshold Concentration ◽  
Atp Depletion ◽  
Resting Potential ◽  
Slow Inward Current ◽  
Embryonic Chick ◽  
Lipid Bilayer Membranes ◽  
Action Potential Plateau ◽  
Kinetics Of ◽  
Potential Plateau

The effects of valinomycin, an agent known to increase the K+ conductance (gK) of lipid bilayer membranes and to be an uncoupler of oxidative phosphorylation, were examined on young (3 days old) and old (15-19 days old) embryonic chick hearts. In the old hearts, valinomycin produced pronounced shortening of the action potential plateau, and often only the spike component remained. The rate of rise of the action potential was usually not affected (slightly diminished sometimes). Addition of dimethylsulfoxide (2 percent), the vehicle for the valinomycin, did not cause shortening of the plateau. The diminution of the plateau by valinomycin at 1 mug/ml was usually obtained after incubation for 1 h; larger doses produced prominent effects within 15 min. The threshold concentration was about 0.1 mug/ml. Cooling, isoproterenol, Ba++, Sr++, and tetraethylammonium partially relengthened the plateau shortened by valinomycin. Lowering of external K+ also lengthened the plateau slightly in the presence of valinomycin. Young embryonic hearts were more resistant to valinomycin, and it was necessary to incubate with 20-40 mug/ml for 1-2 h to produce a significant diminution in plateau. In both young and old hearts, the resting potential was not increased by valinomycin, even though young hearts have a low resting potential (similar to minus 40 mV) mainly because of a low gK. These results suggest that the kinetics of the changes in gK during the action potential plateau may be more greatly affected by valinomycin than the steady-state gK of the resting membrane. In addition to such a direct effect on the sarcolemma, valinomycin could also exert an indirect effect by blocking the slow inward current through ATP depletion.

Selective attenuation by adenosine of arrhythmogenic action of isoproterenol on ventricular myocytes

2001 ◽  
Vol 280 (6) ◽  
pp. H2789-H2795 ◽  
Author(s):  
Yejia Song ◽  
John C. Shryock ◽  
Harm J. Knot ◽  
Luiz Belardinelli
Keyword(s):  
Action Potential ◽  
Receptor Agonist ◽  
Ventricular Myocytes ◽  
Adrenergic Stimulation ◽  
Motion Detector ◽  
Adenosine Receptor Agonist ◽  
Action Potential Plateau ◽  
Delayed Afterdepolarizations ◽  
Isolated Ventricular Myocytes ◽  
Potential Plateau

We examined whether adenosine equally attenuated the stimulatory effects of isoproterenol on arrhythmic activity and twitch shortening of guinea pig isolated ventricular myocytes. Transmembrane voltages and whole cell currents were recorded with patch electrodes, and cell twitch shortening was measured using a video-motion detector. Isoproterenol increased the action potential duration at 50% repolarization (APD50), L-type Ca2+ current [ I Ca(L)], and cell twitch shortening and induced delayed afterdepolarizations (DAD), transient inward current ( I Ti), and aftercontractions. Adenosine attenuated the arrhythmogenic actions of isoproterenol more than it attenuated the effects of isoproterenol on APD50, I Ca(L), or twitch shortening. Adenosine (0.1–100 μmol/l) decreased the amplitude of DADs by 30 ± 6% to 92 ± 5% but attenuated isoproterenol-induced prolongation of the APD50 by only 14 ± 4% to 59 ± 4% and had no effect on the voltage of action potential plateau. Adenosine (30 μmol/l) inhibited I Ti by 91 ± 4% but decreased isoproterenol-stimulated I Ca(L) by only 30 ± 12%. Isoproterenol-induced aftercontractions were abolished by adenosine (10 μmol/l), whereas the amplitude of twitch shortening was not reduced. The effects of adenosine on twitch shortenings and aftercontractions were mimicked by the A1-adenosine receptor agonist CPA ( N 6-cyclopentyladenosine) and by ryanodine. In conclusion, adenosine antagonized the proarrhythmic effect of β-adrenergic stimulation on ventricular myocytes without reducing cell twitch shortening.

scholarly journals Late I Na Blocker GS967 Supresses Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long QT Type 2

2020 ◽  
Vol 13 (8) ◽  
Author(s):  
Jungmin Hwang ◽  
Tae Yun Kim ◽  
Dmitry Terentyev ◽  
Mingwang Zhong ◽  
Anatoli Y. Kabakov ◽  
...  
Keyword(s):  
Action Potential ◽  
Long Qt Syndrome ◽  
Rabbit Model ◽  
Syndrome Type ◽  
Long Qt ◽  
Repolarization Reserve ◽  
Action Potential Plateau ◽  
Qt Syndrome ◽  
Potential Plateau

Background: Long QT syndrome has been associated with sudden cardiac death likely caused by early afterdepolarizations (EADs) and polymorphic ventricular tachycardias (PVTs). Suppressing the late sodium current (I NaL ) may counterbalance the reduced repolarization reserve in long QT syndrome and prevent EADs and PVTs. Methods: We tested the effects of the selective I NaL blocker GS967 on PVT induction in a transgenic rabbit model of long QT syndrome type 2 using intact heart optical mapping, cellular electrophysiology and confocal Ca 2+ imaging, and computer modeling. Results: GS967 reduced ventricular fibrillation induction under a rapid pacing protocol (n=7/14 hearts in control versus 1/14 hearts at 100 nmol/L) without altering action potential duration or restitution and dispersion. GS967 suppressed PVT incidences by reducing Ca 2+ -mediated EADs and focal activity during isoproterenol perfusion (at 30 nmol/L, n=7/12 and 100 nmol/L n=8/12 hearts without EADs and PVTs). Confocal Ca 2+ imaging of long QT syndrome type 2 myocytes revealed that GS967 shortened Ca 2+ transient duration via accelerating Na + /Ca 2+ exchanger (I NCX )-mediated Ca 2+ efflux from cytosol, thereby reducing EADs. Computer modeling revealed that I NaL potentiates EADs in the long QT syndrome type 2 setting through (1) providing additional depolarizing currents during action potential plateau phase, (2) increasing intracellular Na + (Na i ) that decreases the depolarizing I NCX thereby suppressing the action potential plateau and delaying the activation of slowly activating delayed rectifier K + channels (I Ks ), suggesting important roles of I NaL in regulating Na i . Conclusions: Selective I NaL blockade by GS967 prevents EADs and abolishes PVT in long QT syndrome type 2 rabbits by counterbalancing the reduced repolarization reserve and normalizing Na i . Graphic Abstract: A graphic abstract is available for this article.

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