Temperature and relative contributions of Ca transport systems in cardiac myocyte relaxation

1996 ◽  
Vol 270 (5) ◽  
pp. H1772-H1778 ◽  
Author(s):  
J. L. Puglisi ◽  
R. A. Bassani ◽  
J. W. Bassani ◽  
J. N. Amin ◽  
D. M. Bers
Keyword(s):  
Time Course ◽  
Cardiac Myocyte ◽  
Ventricular Myocytes ◽  
Transport Systems ◽  
Effect Of Temperature ◽  
Free Solution ◽  
Tyrode Solution ◽  
Ca Pump ◽  
Ca Transport ◽  
Normal Tyrode Solution

The relative contributions of the different Ca transport systems involved in cardiac relaxation were evaluated at 25 and 35 degrees C in isolated rabbit, ferret, and cat ventricular myocytes during twitches, caffeine-induced contractures in normal Tyrode solution, and caffeine-induced contractures in Na- and Ca-free solution. The time course of intracellular [Ca] decline these contractions in rabbit ventricular myocytes allowed estimates of the relative contributions of the sarcoplasmic reticulum (SR) Ca pump, Na/Ca exchange, sarcolemmal Ca pump, and the mitochondrial calcium uniporter (with the latter two considered together as “slow mechanisms”).The percent contributions of the SR Ca pump, the Na/Ca exchange, and the slow mechanisms were 70, 27 and 3% at 25 degrees C and 74, 23, and 3% at 35 degrees C. Warming from 25 to 35 degrees C decreases twitch contractions in rabbit and ferret myocytes and caffeine-induced contractures in normal Tyrode solution and Na- and Ca-free solution in all species. In contrast, in cat myocytes warming increased twitches, possibly because of a stronger effect of temperature on Ca influx. We conclude that increased temperature accelerates all of the Ca transport systems involved in relaxation. Despite large changes in each Ca transport system with warming, the relative contributions during relaxation remain similar at physiological temperature.

Cardiac myocyte calcium transport in phospholamban knockout mouse: relaxation and endogenous CaMKII effects

1998 ◽  
Vol 274 (4) ◽  
pp. H1335-H1347 ◽  
Author(s):  
Li Li ◽  
Guoxiang Chu ◽  
Evangelia G. Kranias ◽  
Donald M. Bers
Keyword(s):  
Cardiac Myocyte ◽  
Ventricular Myocytes ◽  
Flux Analysis ◽  
Wild Type ◽  
Dependent Protein Kinase ◽  
Ca Transport ◽  
Pump Activity ◽  
Intracellular Ca ◽  
Dependent Protein ◽  
Exchange Activity

Increases in heart rate are accompanied by acceleration of relaxation. This effect is apparent at the single myocyte level and depends on sarcoplasmic reticulum (SR) Ca transport and Ca/calmodulin dependent protein kinase [CaMKII; see R. A. Bassani, A. Mattiazzi, and D. M. Bers. Am. J. Physiol. 268 ( Heart Circ. Physiol. 37): H703–H712, 1995]. Because phosphorylation of phospholamban (PLB) by CaMKII can stimulate SR Ca transport, it is a plausible candidate mechanism. We examined this issue using ventricular myocytes isolated from wild-type (WT) mice and those in which the PLB gene was ablated by gene targeting (PLB-KO). During steady-state (SS) stimulation, twitch relaxation and intracellular Ca concentration ([Ca]i) decline were significantly faster than after a rest in both WT and PLB-KO myocytes. Furthermore, the CaMKII inhibitor KN-93 (1 μM) abolished the stimulation-dependent acceleration of twitch [Ca]i decline in PLB-KO. This indicates that neither PLB nor its phosphorylation are required for the CaMKII-dependent acceleration of the SS twitch [Ca]i decline and relaxation. Other quantitative aspects of Ca transport in WT and PLB-KO myocytes were also examined. As expected, the time constant (τ) of [Ca]i decline during the SS twitch is much faster in PLB-KO than in WT myocytes (112 ± 6 vs. 188 ± 14 ms, P < 0.0001). There was also an increase in SS SR Ca load, based on the change of [Ca]i during rapid caffeine-induced contractures (CafC) with Na/Ca exchange blocked (565 ± 74 nM for WT, 1118 ± 133 nM for PLB-KO, P < 0.01). Accounting for cytosolic Ca buffering, this implies a 37% increase in SR Ca content. The τ for [Ca]idecline of the CafC with Na present indicated slower extrusion by Na/Ca exchange in the PLB-KO mouse (2.2 ± 0.2 s in WT vs. 3.2 ± 0.2 s in PLB-KO, P < 0.01), although exchanger protein expression was unchanged. Integrated Ca flux analysis in WT and PLB-KO myocytes, respectively, shows that 90 and 96% of Ca during twitch relaxation is removed by the SR Ca-ATPase, 9 and 3.4% by Na/Ca exchange, and 0.5 and 0.1% by slow mechanisms (mitochondria Ca uniporter and sarcolemmal Ca-ATPase). We conclude that the PLB-KO myocytes retain a CaMKII-dependent acceleration of SS twitch [Ca]i decline. The PLB-KO (vs. WT) myocytes also have higher SR Ca pump activity, higher SR Ca load, and reduced Na/Ca exchange activity.

Na+-Ca2+ exchange in regulation of contractility in canine cardiac Purkinje fibers

1988 ◽  
Vol 255 (3) ◽  
pp. C278-C290 ◽  
Author(s):  
J. K. Sonn ◽  
C. O. Lee
Keyword(s):  
Transmembrane Potential ◽  
The Other ◽  
Free Solution ◽  
Tyrode Solution ◽  
Purkinje Fibers ◽  
Resting Tension ◽  
Intracellular Na Activity ◽  
Cardiac Purkinje Fibers ◽  
Constant Rate ◽  
Normal Tyrode Solution

To study Na+-Ca2+ exchange, intracellular Na+ activity (aiNa), twitch tension, and transmembrane potential were simultaneously measured in canine cardiac Purkinje fibers driven at a constant rate (1 Hz) in the absence and presence of strophanthidin (5 X 10(-7) M) at normal, low, and high extracellular [Na+] ([Na+]o) or [Ca2+] ([Ca2+]o). Intracellular Ca2+ activity (aiCa) of the fibers was also measured in a normal Tyrode solution. Reductions of [Na+]o by 20, 40, and 60% decreased the ratio of extracellular Na+ activity (aoNa) and aiNa in the steady state but steeply increased twitch tension. This finding is consistent with the view that a decrease in aoNa/aiNa increases intracellular Ca2+ through Na+-Ca2+ exchange. In further agreement with this view, a Na+-free solution virtually depleted intracellular Na+ and increased the resting tension of the fibers. The slope of the relation of the logs of twitch tension and aiNa that was determined at normal [Na+]o and [Ca2+]o may reflect the properties of the Na+-Ca2+ exchange. Slope of log tension-aiNa relationship decreased when reducing [Na+]o or increasing [Ca2+]o had decreased the level of aiNa. On the other hand, the slope increased when a rise in [Na+]o or a reduction in [Ca2+]o had increased the level of aiNa. These results indicate that as the aiNa level increased, slope of tension-aiNa relation increased, which suggests that Na+-Ca2+ exchange may depend on level of aiNa.(ABSTRACT TRUNCATED AT 250 WORDS)

Na+–K+ transport, motility and tegumental membrane potential in adult male Schistosoma mansoni

Parasitology ◽  
1981 ◽  
Vol 82 (1) ◽  
pp. 97-109 ◽  
Author(s):  
R. H. Fetterer ◽  
R. A. Pax ◽  
J. L. Bennett
Keyword(s):  
Membrane Potential ◽  
Schistosoma Mansoni ◽  
Adult Male ◽  
Time Course ◽  
Muscle Tension ◽  
Transport Systems ◽  
Effect Of Temperature ◽  
Bathing Medium ◽  
Tension Development ◽  
Tension Increase

SUMMARYOuabain applied to adult male Schistosoma mansoni causes a large, non-reversible tension increase of the parasite's musculature and elimination of spontaneous contractions. The tension increase and the time-course of tension development caused by ouabain are dose dependent with significant effects obtained at 3 × 10−6m. Digoxin and digoxigenin act in a similar manner with a relative potency of ouabain ≃ digoxin > digoxigenin. Lowered temperature as well as substitution of Li+ for Na+ increases muscle tension. The membrane potential recorded from the ventral tegument is also affected by treatments which interact with Na+–K+ transport systems. Ouabain (0·1 mm) causes a rapid depolarization without a significant effect on membrane resistance. The tegument is depolarized by temperatures below 30 °C. The effect of temperature is readily reversible and the temperature sensitivity is eliminated by pretreatment with ouabain. Substitution of Li+ for Na+ also causes a depolarization of the tegument. Tracer experiments show both an increase in Na+ and a decrease in K+ in the parasite within 10 min after treatment with ouabain (1 × 10−5m). Decreasing temperature of the bathing medium also causes an accumulation of Na+ as well as a decrease in the animals. The above results indicate a significant role for active Na+–K+ transport in muscle contraction and in maintenance of the tegumental membrane potential. The data also suggest that the Na+–K+ transport in S. mansoni may be electrogenic.

Kinetics of [Ca]i decline in cardiac myocytes depend on peak [Ca]i

1995 ◽  
Vol 268 (1) ◽  
pp. C271-C277 ◽  
Author(s):  
D. M. Bers ◽  
J. R. Berlin
Keyword(s):  
Ventricular Myocytes ◽  
Transport Rate ◽  
Transport Systems ◽  
Ca Transport ◽  
Rat Hearts ◽  
Wide Range ◽  
Intracellular Ca ◽  
Rate Of Decline ◽  
Kinetics Of ◽  
Peak Value

The rate of decline of free intracellular Ca concentration ([Ca]i) is a potentially useful index of the function of Ca transport systems. However, interpretations of these results may depend on multiple Ca transport systems and interaction with intracellular Ca binding sites. We measured [Ca]i in voltage-clamped ventricular myocytes isolated from rat hearts using indo 1 fluorescence. Conditions were chosen where [Ca]i decline was expected to depend almost exclusively on the sarcoplasmic reticulum Ca pump. The half time of [Ca]i decline (t1/2) decreased as the amplitude of the intracellular Ca (Cai) transient increased. This is not the result that would be expected from a transport system where the transport rate is a linear function of free [Ca]i. In this case the time constant of [Ca]i decline (tau) should be independent of the peak value of [Ca]i. This is also true if linear buffering of Cai is included. We develop a simple but more realistic theoretical framework where Ca transport rate and Ca binding both depend on free [Ca]i with Michaelis-Menten type functions. We demonstrate that the observed decline in apparent tau with increasing peak [Ca]i is entirely expected on theoretical grounds and over a wide range of characteristics for Ca transport and binding. We conclude that one cannot draw inferences about the intrinsic Ca transport function based on tau values unless the Cai transient has a comparable size.

Dual effects of external magnesium on action potential duration in guinea pig ventricular myocytes

1995 ◽  
Vol 268 (6) ◽  
pp. H2321-H2328 ◽  
Author(s):  
S. Zhang ◽  
T. Sawanobori ◽  
H. Adaniya ◽  
Y. Hirano ◽  
M. Hiraoka
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Decay Time ◽  
Action Potential Duration ◽  
Time Course ◽  
Ventricular Myocytes ◽  
Membrane Surface ◽  
Surface Charges ◽  
Whole Cell Patch Clamp ◽  
K Current

Effects of extracellular magnesium (Mg2+) on action potential duration (APD) and underlying membrane currents in guinea pig ventricular myocytes were studied by using the whole cell patch-clamp method. Increasing external Mg2+ concentration [Mg2+]o) from 0.5 to 3 mM produced a prolongation of APD at 90% repolarization (APD90), whereas 5 and 10 mM Mg2+ shortened it. [Mg2+]o, at 3 mM or higher, suppressed the delayed outward K+ current and the inward rectifier K+ current. Increases in [Mg2+]o depressed the peak amplitude and delayed the decay time course of the Ca2+ current (ICa), the latter effect is probably due to the decrease in Ca(2+)-induced inactivation. Thus 3 mM Mg2+ suppressed the peak ICa but increased the late ICa amplitude at the end of a 200-ms depolarization pulse, whereas 10 mM Mg2+ suppressed both components. Application of 10 mM Mg2+ shifted the voltage-dependent activation and inactivation by approximately 10 mV to more positive voltage due to screening the membrane surface charges. Application of manganese (1-5 mM) also caused dual effects on APD90, similar to those of Mg2+, and suppressed the peak ICa with slowed decay. These results suggest that the dual effects of Mg2+ on APD in guinea pig ventricular myocytes can be, at least in part, explained by its action on ICa with slowed decay time course in addition to suppressive effects on K+ currents.

p38 MAP kinase inhibitor reverses stress-induced cardiac myocyte dysfunction

2005 ◽  
Vol 98 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Hong Kan ◽  
Dale Birkle ◽  
Abnash C. Jain ◽  
Conard Failinger ◽  
Sherry Xie ◽  
...  
Keyword(s):  
Map Kinase ◽  
Cardiac Myocyte ◽  
Kinase Inhibitor ◽  
Ventricular Myocytes ◽  
Myocardial Dysfunction ◽  
P38 Map Kinase ◽  
Border Detection ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Fractional Shortening

Stress is gaining increasing acceptance as an independent risk factor contributing to adverse cardiovascular outcomes. Potential mechanisms responsible for the deleterious effects of stress on the development and progression of cardiovascular disease remain to be elucidated. An established animal model of stress in humans is the prenatally stressed (PS) rat. We stressed rats in their third trimester of pregnancy by daily injections of saline and moving from cage to cage. Male offspring of these stressed dams (PS) and age-matched male control offspring (control) were further subjected to restraint stress (R) at 6 and 7 wk of age. Echocardiography revealed a significant decrease in fractional shortening in PS + R vs. controls + R (45.8 ± 3.9 vs. 61.9 ± 2.4%, PS + R vs. controls + R; P < 0.01; n = 12). Isolated adult rat ventricular myocytes from PS + R also revealed diminished fractional shortening (6.7 ± 0.8 vs. 12.7 ± 1.1%, PS + R vs. controls + R; P < 0.01; n = 24) and blunted inotropic responses to isoproterenol ( P < 0.01; n = 24) determined by automated border detection. The p38 mitogen-activated protein (MAP) kinase inhibitor SB-203580 blocked p38 MAP kinase phosphorylation, reversed the depression in fractional shortening, and partially ameliorated the blunted adrenergic signaling seen in adult rat ventricular myocytes from PS + R. Phosphorylation of p38 MAP kinase in cardiac myocytes by stress may be sufficient to lead to myocardial dysfunction in animal models and possibly humans.

scholarly journals Positive Inotropic Effects of ATP Released via the Maxi-Anion Channel in Langendorff-Perfused Mouse Hearts Subjected to Ischemia-Reperfusion

2021 ◽  
Vol 9 ◽  
Author(s):  
Hiroshi Matsuura ◽  
Akiko Kojima ◽  
Yutaka Fukushima ◽  
Yu Xie ◽  
Xinya Mi ◽  
...  
Keyword(s):  
Contractile Function ◽  
Organic Anion ◽  
Left Ventricular ◽  
Transient Increase ◽  
Tyrode Solution ◽  
Inotropic Effects ◽  
Cl Channel ◽  
Short Period ◽  
Cl Channels ◽  
Normal Tyrode Solution

The organic anion transporter SLCO2A1 constitutes an essential core component of the ATP-conductive large-conductance anion (Maxi-Cl) channel. Our previous experiments using Langendorff-perfused mouse hearts showed that the Maxi-Cl channel contributes largely to the release of ATP into the coronary effluent observed during 10-min reperfusion following a short period (6 min) of oxygen-glucose deprivation. The present study examined the effect of endogenous ATP released via Maxi-Cl channels on the left ventricular contractile function of Langendorff-perfused mouse hearts, using a fluid-filled balloon connected to a pressure transducer. After the initial 30-min stabilization period, the heart was then perfused with oxygen-glucose-deprived Tyrode solution for 6 min, which was followed by a 10-min perfusion with oxygenated normal Tyrode solution in the absence and presence of an ATP-hydrolyzing enzyme, apyrase, and/or an adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). In the absence of apyrase and DPCPX, the left ventricular developed pressure (LVDP) decreased from a baseline value of 72.3 ± 7.1 to 57.5 ± 5.5 mmHg (n = 4) at the end of 6-min perfusion with oxygen-glucose-deprived Tyrode solution, which was followed by a transient increase to 108.5 ± 16.5 mmHg during subsequent perfusion with oxygenated normal Tyrode solution. However, in the presence of apyrase and DPCPX, the LVDP decreased to the same degree during 6-min perfusion with oxygen-glucose-deprived Tyrode solution, but failed to exhibit a transient increase during a subsequent perfusion with oxygenated normal Tyrode solution. These results strongly suggest that endogenous ATP released through Maxi-Cl channels contributes to the development of transient positive inotropy observed during reperfusion after short-period hypoxia/ischemia in the heart.

scholarly journals Using naturalistic incubation temperatures to demonstrate how variation in the timing and continuity of heat wave exposure influences phenotype

2020 ◽  
Vol 287 (1932) ◽  
pp. 20200992 ◽  
Author(s):  
Anthony T. Breitenbach ◽  
Amanda W. Carter ◽  
Ryan T. Paitz ◽  
Rachel M. Bowden
Keyword(s):  
Heat Wave ◽  
Time Course ◽  
Heat Waves ◽  
Heat Exposure ◽  
Effect Of Temperature ◽  
Similar Time ◽  
Expression Of Genes ◽  
Short Period ◽  
The Face ◽  
Temperature Exposure

Most organisms are exposed to bouts of warm temperatures during development, yet we know little about how variation in the timing and continuity of heat exposure influences biological processes. If heat waves increase in frequency and duration as predicted, it is necessary to understand how these bouts could affect thermally sensitive species, including reptiles with temperature-dependent sex determination (TSD). In a multi-year study using fluctuating temperatures, we exposed Trachemys scripta embryos to cooler, male-producing temperatures interspersed with warmer, female-producing temperatures (heat waves) that varied in either timing during development or continuity and then analysed resulting sex ratios. We also quantified the expression of genes involved in testis differentiation ( Dmrt1 ) and ovary differentiation ( Cyp19A1 ) to determine how heat wave continuity affects the expression of genes involved in sexual differentiation. Heat waves applied during the middle of development produced significantly more females compared to heat waves that occurred just 7 days before or after this window, and even short gaps in the continuity of a heat wave decreased the production of females. Continuous heat exposure resulted in increased Cyp19A1 expression while discontinuous heat exposure failed to increase expression in either gene over a similar time course. We report that even small differences in the timing and continuity of heat waves can result in drastically different phenotypic outcomes. This strong effect of temperature occurred despite the fact that embryos were exposed to the same number of warm days during a short period of time, which highlights the need to study temperature effects under more ecologically relevant conditions where temperatures may be elevated for only a few days at a time. In the face of a changing climate, the finding that subtle shifts in temperature exposure result in substantial effects on embryonic development becomes even more critical.

Outward currents in normal and hypertrophied feline ventricular myocytes

1989 ◽  
Vol 256 (5) ◽  
pp. H1450-H1461 ◽  
Author(s):  
R. B. Kleiman ◽  
S. R. Houser
Keyword(s):  
Time Course ◽  
Ventricular Myocytes ◽  
Pressure Overload ◽  
Negative Slope ◽  
Inward Rectification ◽  
Delayed Rectifier ◽  
Outward Currents ◽  
K Current ◽  
Prolongation Of Action Potential ◽  
The Right

The properties of the inward rectifier K current (IK1) and the delayed rectifier K current (IK) were studied in single feline myocytes isolated from the right ventricle of normal cats and cats with experimentally induced right ventricular hypertrophy (RVH). IK1 demonstrated time-dependent decay during hyperpolarizations and showed inward rectification with a prominent negative-slope region between -30 and -10 mV. Both IK1 and IK was carried primarily by K ions. The activation of IK during depolarizations followed a monoexponential time course, whereas the deactivation of IK tail currents was either mono- or biexponential depending on the repolarization potential. IK showed marked rectification at positive potentials. A comparison of these currents in normal and hypertrophy myocytes revealed that in RVH the magnitude of IK1 is increased, whereas the magnitude of IK is decreased. IK showed steeper rectification, had slower activation, and had more rapid deactivation in RVH. These abnormalities of the IK may contribute to the prolongation of action potential duration, which characterizes pressure-overload cardiac hypertrophy.

Effect of reduced Na gradient on electrical activity in isolated bovine and feline ventricular myocytes

1988 ◽  
Vol 66 (2) ◽  
pp. 222-232 ◽  
Author(s):  
Magda Horackova ◽  
Andrzej Beresewicz ◽  
Gerrit Isenberg
Keyword(s):  
Electrical Activity ◽  
Ventricular Myocytes ◽  
Ionic Current ◽  
Outward Current ◽  
Free Solution ◽  
Initial Part ◽  
Inward Current ◽  
Ca Inward Current ◽  
Sudden Decrease ◽  
K Currents

We have studied changes in electrical activity resulting from abrupt alterations of the Na gradient, using ventricular myocytes isolated from feline and bovine hearts. Attempting to investigate the ionic current possibly generated by Na–Ca exchange, we studied the effects of the changes in [Na]o in the presence of 20 mM CsCl to inhibit K currents. To facilitate the effect of Cs, we also used a K-free solution and a patch electrode filled with 150 mM cesium glutamate. The application of 20 mM Nao resulted in hyperpolarization and the action potential duration was reduced. Under voltage clamp, 20 or 45 mM Nao generated an outward current at all membrane potentials investigated. The initial part (100–200 ms) of this current was only partially inhibited by 5 mM NiCl2 which is known to fully block the Ca inward current. However, the outward current generated by the reduced [Na]o was fully inhibited by 20 mM MnCl2 (which presumably inhibits Na–Ca exchange). Our observations extend the work on multicellular cardiac preparations indicating that the outward current elicited by a sudden decrease in Na gradient could be generated by Na–Ca exchange. Although the characteristics of this outward current support certain concepts of the Na–Ca exchange in cardiac muscle, we cannot at present exclude a contribution of other membrane current(s).

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