scholarly journals Temperature- and external K+-dependence of electrical excitation in ventricular myocytes of cod-like fishes

2019 ◽  
pp. jeb.193607 ◽  
Author(s):  
Denis V. Abramochkin ◽  
Jaakko Haverinen ◽  
Yuri A. Mitenkov ◽  
Matti Vornanen
Keyword(s):  
Ventricular Myocytes ◽  
Electrical Excitation ◽  
External K

Existence of a transient outward K+ current in guinea pig cardiac myocytes

2000 ◽  
Vol 279 (1) ◽  
pp. H130-H138 ◽  
Author(s):  
Gui-Rong Li ◽  
Baofeng Yang ◽  
Haiying Sun ◽  
Clive M. Baumgarten
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Resting Potential ◽  
Transient Outward Current ◽  
Time Constants ◽  
Zero Current ◽  
Steady State Inactivation ◽  
K Current ◽  
External K

A novel transient outward K+current that exhibits inward-going rectification ( I to.ir) was identified in guinea pig atrial and ventricular myocytes. I to.ir was insensitive to 4-aminopyridine (4-AP) but was blocked by 200 μmol/l Ba2+or removal of external K+. The zero current potential shifted 51–53 mV/decade change in external K+. I to.ir density was twofold greater in ventricular than in atrial myocytes, and biexponential inactivation occurs in both types of myocytes. At −20 mV, the fast inactivation time constants were 7.7 ± 1.8 and 6.1 ± 1.2 ms and the slow inactivation time constants were 85.1 ± 14.8 and 77.3 ± 10.4 ms in ventricular and atrial cells, respectively. The midpoints for steady-state inactivation were −36.4 ± 0.3 and −51.6 ± 0.4 mV, and recovery from inactivation was rapid near the resting potential (time constants = 7.9 ± 1.9 and 8.8 ± 2.1 ms, respectively). I to.ir was detected in Na+-containing and Na+-free solutions and was not blocked by 20 nmol/l saxitoxin. Action potential clamp revealed that I to.ir contributed an outward current that activated rapidly on depolarization and inactivated by early phase 2 in both tissues. Although it is well known that 4-AP-sensitive transient outward current is absent in guinea pig, this Ba2+-sensitive and 4-AP-insensitive K+ current has been overlooked.

scholarly journals Induced cardiac pacemaker cells survive metabolic stress owing to their low metabolic demand

2019 ◽  
Vol 51 (9) ◽  
pp. 1-12 ◽  
Author(s):  
Jin-mo Gu ◽  
Sandra I. Grijalva ◽  
Natasha Fernandez ◽  
Elizabeth Kim ◽  
D. Brian Foster ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Cardiac Pacemaker ◽  
Metabolic Stress ◽  
Mitochondrial Morphology ◽  
Electrical Excitation ◽  
Metabolic Demand ◽  
Pacemaker Cells ◽  
Membrane Fusion Protein ◽  
Mitochondrial Inner Membrane ◽  
Metabolic Stresses

Abstract Cardiac pacemaker cells of the sinoatrial node initiate each and every heartbeat. Compared with our understanding of the constituents of their electrical excitation, little is known about the metabolic underpinnings that drive the automaticity of pacemaker myocytes. This lack is largely owing to the scarcity of native cardiac pacemaker myocytes. Here, we take advantage of induced pacemaker myocytes generated by TBX18-mediated reprogramming (TBX18-iPMs) to investigate comparative differences in the metabolic program between pacemaker myocytes and working cardiomyocytes. TBX18-iPMs were more resistant to metabolic stresses, exhibiting higher cell viability upon oxidative stress. TBX18-induced pacemaker myocytes (iPMs) expensed a lower degree of oxidative phosphorylation and displayed a smaller capacity for glycolysis compared with control ventricular myocytes. Furthermore, the mitochondria were smaller in TBX18-iPMs than in the control. We reasoned that a shift in the balance between mitochondrial fusion and fission was responsible for the smaller mitochondria observed in TBX18-iPMs. We identified a mitochondrial inner membrane fusion protein, Opa1, as one of the key mediators of this process and demonstrated that the suppression of Opa1 expression increases the rate of synchronous automaticity in TBX18-iPMs. Taken together, our data demonstrate that TBX18-iPMs exhibit a low metabolic demand that matches their mitochondrial morphology and ability to withstand metabolic insult.

Transient outward current carried by inwardly rectifying K+ channels in guinea pig ventricular myocytes dialyzed with low-K+ solution

2004 ◽  
Vol 287 (5) ◽  
pp. C1396-C1403 ◽  
Author(s):  
Pavel Zhabyeyev ◽  
Tatsuya Asai ◽  
Sergey Missan ◽  
Terence F. McDonald
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Transient Outward Current ◽  
K Channels ◽  
Voltage Gated ◽  
Voltage Gated Channels ◽  
Inwardly Rectifying ◽  
Low K ◽  
External K

There have been periodic reports of nonclassic (4-aminopyridine insensitive) transient outward K+ current in guinea pig ventricular myocytes, with the most recent one describing a novel voltage-gated inwardly rectifying type. In the present study, we have investigated a transient outward current that overlaps inward Ca2+ current ( ICa,L) in myocytes dialyzed with 10 mM K+ solution and superfused with Tyrode’s solution. Although depolarizations from holding potential ( Vhp) −40 to 0 mV elicited relatively small inward ICa,L in these myocytes, removal of external K+ or addition of 0.2 mM Ba2+ more than doubled the amplitude of the current. The basis of the enhancement of ICa,L was the suppression of a large transient outward K+ current. Similar enhancement was observed when Vhp was moved to −80 mV and test depolarizations were preceded by short prepulses to −40 mV. Investigation of the time and voltage properties of the outward K+ transient indicated that it was inwardly rectifying and unlikely to be carried by voltage-gated channels. The outward transient was attenuated in myocytes dialyzed with high-Mg2+ solution, accelerated in myocytes dialyzed with 100 μM spermine solution, and abolished with time in myocytes dialyzed with ATP-free solution. These and other findings suggest that the outward transient is a component of classic “time-independent” inwardly rectifying K+ current.

scholarly journals Steady-state current-voltage relationship of the Na/K pump in guinea pig ventricular myocytes.

1989 ◽  
Vol 94 (3) ◽  
pp. 511-537 ◽  
Author(s):  
D C Gadsby ◽  
M Nakao
Keyword(s):  
Steady State ◽  
Guinea Pig ◽  
Rate Constants ◽  
Ventricular Myocytes ◽  
Pump Current ◽  
Membrane Current ◽  
Negative Slope ◽  
Current Voltage ◽  
State Cycle ◽  
External K

Whole-cell currents were recorded in guinea pig ventricular myocytes at approximately 36 degrees C before, during, and after exposure to maximally effective concentrations of strophanthidin, a cardiotonic steroid and specific inhibitor of the Na/K pump. Wide-tipped pipettes, in combination with a device for exchanging the solution inside the pipette, afforded reasonable control of the ionic composition of the intracellular solution and of the membrane potential. Internal and external solutions were designed to minimize channel currents and Na/Ca exchange current while sustaining vigorous forward Na/K transport, monitored as strophanthidin-sensitive current. 100-ms voltage pulses from the -40 mV holding potential were used to determine steady-state levels of membrane current between -140 and +60 mV. Control experiments demonstrated that if the Na/K pump cycle were first arrested, e.g., by withdrawal of external K, or of both internal and external Na, then neither strophanthidin nor its vehicle, dimethylsulfoxide, had any discernible effect on steady-state membrane current. Further controls showed that, with the Na/K pump inhibited by strophanthidin, membrane current was insensitive to changes of external [K] between 5.4 and 0 mM and was little altered by changing the pipette [Na] from 0 to 50 mM. Strophanthidin-sensitive current therefore closely approximated Na/K pump current, and was virtually free of contamination by current components altered by the changes in extracellular [K] and intracellular [Na] expected to accompany pump inhibition. The steady-state Na/K pump current-voltage (I-V) relationship, with the pump strongly activated by 5.4 mM external K and 50 mM internal Na (and 10 mM ATP), was sigmoid in shape with a steep positive slope between about 0 and -100 mV, a less steep slope at more negative potentials, and an extremely shallow slope at positive potentials; no region of negative slope was found. That shape of I-V relationship can be generated by a two-state cycle with one pair of voltage-sensitive rate constants and one pair of voltage-insensitive rate constants: such a two-state scheme is a valid steady-state representation of a multi-state cycle that includes only a single voltage-sensitive step.

Isoproterenol directly stimulates the Na+-K+ pump in isolated cardiac myocytes

1986 ◽  
Vol 251 (1) ◽  
pp. H218-H225 ◽  
Author(s):  
M. Desilets ◽  
C. M. Baumgarten
Keyword(s):  
Steady State ◽  
Time Course ◽  
Ventricular Myocytes ◽  
Rabbit Heart ◽  
Relative Effect ◽  
Beta Agonist ◽  
Intracellular Na Activity ◽  
Pump Activity ◽  
Isolated Cardiac Myocytes ◽  
External K

It has been suggested that catecholamines directly stimulate Na+-K+ pump activity in heart; however, these studies on multicellular preparations are confounded by possible alterations of extracellular K+ concentrations ([K+]o). We reinvestigated this problem by studying the effect of the beta-agonist isoproterenol (Iso) on intracellular Na+ activity (aiNa) in ventricular myocytes enzymatically isolated from rabbit heart. In 5 mM [K+]o, 0.1 microM Iso caused a 24.6 +/- 2.0% decrease of aiNa. Exposure to 1 microM Iso only caused a small additional decrease (27.8 +/- 2.4%), while a diminution of aiNa could already be noticed with only 10 nM Iso (12.8 +/- 1.9% diminution). Myocytes superfused with 15 mM [K+]o also exhibited a significant decrease of aiNa (22.9 +/- 3.6%) when exposed to 0.1 microM Iso. These data argue that accumulation of external K+ does not account for the effect of Iso on steady-state aiNa as postulated by Gadsby (Nature Lond. 306: 691-693, 1983). Furthermore, aiNa in myocytes superfused with 1.5 mM [K+]o decreased by only 8.7% on addition of 0.1 microM Iso. The latter observation suggests that the beta-agonist effect on aiNa regulation is directly or indirectly dependent on membrane potential and/or aiNa. Finally, kinetic analysis of the effect of 1 microM Iso on the decrease in aiNa on changing [K+]o from 1.5 to 5 mM demonstrated that the time course of aiNa recovery was accelerated by a factor of 1.9. This readily suggests that active Na+ transport is directly stimulated by Iso. The much greater relative effect of Iso on the time constant than on steady-state aiNa further indicates that Iso may also increase passive Na+ influx.

Positive inotropic effects of ouabain in isolated cat ventricular myocytes in sodium-free conditions

2002 ◽  
Vol 283 (5) ◽  
pp. H2045-H2053 ◽  
Author(s):  
Manabu Nishio ◽  
Stuart W. Ruch ◽  
J. Andrew Wasserstrom
Keyword(s):  
Atpase Activity ◽  
Voltage Clamp ◽  
Ventricular Myocytes ◽  
Inotropic Response ◽  
Inotropic Effects ◽  
Cellular Effects ◽  
Positive Inotropic Effects ◽  
Intracellular Ca ◽  
Atpase Inhibition ◽  
External K

The inotropic and toxic effects of cardiac steroids are thought to result from Na+-K+-ATPase inhibition, with elevated intracellular Na+(Na[Formula: see text])causing increased intracellular Ca2+(Ca[Formula: see text]) via Na-Ca exchange. We studied the effects of ouabain on cat ventricular myocytes in Na+-free conditions where the exchanger is inhibited. Cell shortening and Ca[Formula: see text] transients (with fluo 4-AM fluorescence) were measured under voltage clamp during exposure to Na+-free solutions [LiCl or N-methyl-d-glucamine (NMDG) replacement]. Ouabain enhanced contractility by 121 ± 55% at 1 μmol/l ( n = 11) and 476 ± 159% at 3 μmol/l ( n = 8) (means ± SE). Ca[Formula: see text] transient amplitude was also increased. The inotropic effects of ouabain were retained even after pretreatment with saxitoxin (5 μmol/l) or changing the holding potential to −40 mV (to inactivate Na+ current). Similar results were obtained with both Li+ and NMDG replacement and in the absence of external K+, indicating that ouabain produced positive inotropy in the absence of functional Na-Ca exchange and Na+-K+-ATPase activity. In contrast, ouabain had no inotropic response in rat ventricular myocytes (10–100 μmol/l). Finally, ouabain reversibly increased Ca2+overload toxicity by accelerating the rate of spontaneous aftercontractions ( n = 13). These results suggest that the cellular effects of ouabain on the heart may include actions independent of Na+-K+-ATPase inhibition, Na-Ca exchange, and changes in Na[Formula: see text].

CARP Plays a Key Role in Cellular Growth Under Hypertrophic Stimuli in Neonatal Rat Ventricular Myocytes

2013 ◽  
Vol 9 ◽  
Author(s):  
Tara A Shrout
Keyword(s):  
Gene Expression ◽  
Ventricular Myocytes ◽  
Cellular Growth ◽  
Neonatal Rat ◽  
Transcriptional Level ◽  
Dual Nature ◽  
Hypertrophic Growth ◽  
Rat Ventricular Myocytes ◽  
Neonatal Rat Ventricular Myocytes ◽  
Over Time

Cardiac hypertrophy is a growth process that occurs in response to stress stimuli or injury, and leads to the induction of several pathways to alter gene expression. Under hypertrophic stimuli, sarcomeric structure is disrupted, both as a consequence of gene expression and local changes in sarcomeric proteins. Cardiac-restricted ankyrin repeat protein (CARP) is one such protein that function both in cardiac sarcomeres and at the transcriptional level. We postulate that due to this dual nature, CARP plays a key role in maintaining the cardiac sarcomere. GATA4 is another protein detected in cardiomyocytes as important in hypertrophy, as it is activated by hypertrophic stimuli, and directly binds to DNA to alter gene expression. Results of GATA4 activation over time were inconclusive; however, the role of CARP in mediating hypertrophic growth in cardiomyocytes was clearly demonstrated. In this study, Neonatal Rat Ventricular Myocytes were used as a model to detect changes over time in CARP and GATA4 under hypertrophic stimulation by phenylephrine and high serum media. Results were detected by analysis of immunoblotting. The specific role that CARP plays in mediating cellular growth under hypertrophic stimuli was studied through immunofluorescence, which demonstrated that cardiomyocyte growth with hypertrophic stimulation was significantly blunted when NRVMs were co-treated with CARP siRNA. These data suggest that CARP plays an important role in the hypertrophic response in cardiomyocytes.

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