Inhibition of rest potentiation in canine ventricular muscle by BAY K 8644: comparison with caffeine

Rest potentiation, believed to be due to increased utilization of sarcoplasmic reticular calcium, was converted to rest depression by BAY K 8644 (1 microM). Plateau height and duration of the postrest beat were enhanced by BAY K 8644, suggesting an enhancement of extracellular calcium entry. Caffeine (3 mM) also produced depression at all rest intervals, although to a lesser extent than BAY K 8644. Compared with BAY K 8644, treatment with caffeine resulted in an elevation of plateau amplitude and a shortening of action potential duration. Action potential configuration changes induced by rest were unaltered by caffeine despite reduction in rest potentiation. Caffeine-induced rest depression was associated with an increase in the time to peak tension. This was not observed with BAY K 8644. Treatment with both caffeine (3 mM) and BAY K 8644 (1 microM) greatly prolonged time to peak tension. Action potential duration and plateau height were either maintained or increased. Less rest depression was observed with the combination than with either agent alone. These results suggest that 1) BAY K 8644 and caffeine inhibit rest potentiation by different mechanisms, and 2) caffeine-induced inhibition of calcium uptake by the sarcoplasmic reticulum may enhance the effect of BAY K 8644-induced increase in calcium influx on the contractile apparatus.

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Inhibition by theophylline of the early component of canine ventricular contraction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1982.242.3.h349 ◽

1982 ◽

Vol 242 (3) ◽

pp. H349-H358

Author(s):

M. Endoh ◽

T. Iijima ◽

S. Motomura

Keyword(s):

Mechanical Characteristics ◽

Calcium Influx ◽

Myocardial Cell ◽

Ventricular Muscle ◽

Late Component ◽

Ventricular Contraction ◽

Early Component ◽

Peak Tension ◽

Time To Peak ◽

Plateau Potential

Changes in mechanical characteristics of the isolated canine ventricular muscle were investigated during interaction of isoproterenol with theophylline or caffeine. An early and a late component with time to peak tension of 80 and 150 ms, respectively, were differentiated in a single contraction of the muscle stimulated at 0.5 Hz at 37 degrees C during the interaction of isoproterenol and theophylline, or isoproterenol and caffeine. Isoproterenol increased preferentially the early component and affected only slightly the late one. Theophylline or caffeine elevated the early component less than the late one. In the presence of theophylline + isoproterenol or caffeine + isoproterenol the peak tension was achieved by a late component, whereas the increase in the early one induced by isoproterenol in 3 X 10(-7) M and higher was depressed significantly. During the interaction the rate of twitch relaxation was accelerated further rather than depressed. Changes in action potential indicate that the calcium influx via the myocardial cell membrane during depolarization was increased: the peak plateau potential was significantly elevated by theophylline alone and further by theophylline + isoproterenol. These results indicate that theophylline and caffeine (2 mM) may act intracellularly to inhibit the isoproterenol-induced promotion of the early component without impairing the isoproterenol-induced acceleration of relaxation in the canine ventricular muscle.

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Acetate-induced depression of electrical and contractile activity in normoxic and hypoxic guinea pig papillary muscle

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-118 ◽

1989 ◽

Vol 67 (7) ◽

pp. 734-739

Author(s):

Hideharu Hayashi ◽

Hajime Terada ◽

Alexander Kholopov ◽

Terence F. McDonald

Keyword(s):

Guinea Pig ◽

Action Potential ◽

Action Potential Duration ◽

Contractile Activity ◽

High Energy ◽

Factors Affecting ◽

Resting Tension ◽

Tension Increase ◽

Action Potential Shortening ◽

Action Potential Configuration

The action potential configuration, developed tension, and resting tension were monitored in normoxic and hypoxic guinea pig papillary muscles superfused with solutions containing no substrate, glucose, or acetate (1–10 mM). In normoxic muscle, acetate provoked a concentration-dependent transient depression of the action potential duration and force of contraction, depression was maximal after 10–30 min, and recovery was complete after 90–120 min. In hypoxic muscle, acetate accelerated functional rundown (action potential shortening, decline of developed tension, increase in resting tension). Because rundown in hypoxic muscle was sensitive to factors affecting glycolysis (moderated by external glucose; accentuated by 2-deoxyglucose), the accentuated rundown with acetate may be accounted for by a partial block of glycolysis. However, block of glycolysis cannot explain the acetate-induced transient depression in normoxic muscle, since the depression was enhanced in normoxic muscle with 2-deoxyglucose-blocked glycolysis. We suggest that the transient depression is due to a transient depression of high energy nucleotides with consequent effects on ionic currents.Key words: acetate, action potential duration, 2-deoxyglucose, hypoxia, ATP.

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Calcium influx through If channels in rat ventricular myocytes

AJP Cell Physiology ◽

10.1152/ajpcell.00598.2005 ◽

2007 ◽

Vol 292 (3) ◽

pp. C1147-C1155 ◽

Cited By ~ 27

Author(s):

Xiao Yu ◽

Xiao-Wei Chen ◽

Peng Zhou ◽

Lijun Yao ◽

Tao Liu ◽

...

Keyword(s):

Action Potential ◽

Cardiac Myocytes ◽

Action Potential Duration ◽

Channel Blocker ◽

Ventricular Myocytes ◽

Spontaneously Hypertensive Rat ◽

Calcium Influx ◽

Hek293 Cells ◽

Hcn Channels ◽

Rat Ventricular Myocytes

The hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, or cardiac ( If)/neuronal ( Ih) time- and voltage-dependent inward cation current channels, are conventionally considered as monovalent-selective channels. Recently we discovered that calcium ions can permeate through HCN4 and Ih channels in neurons. This raises the possibility of Ca2+ permeation in If, the Ih counterpart in cardiac myocytes, because of their structural homology. We performed simultaneous measurement of fura-2 Ca2+ signals and whole cell currents produced by HCN2 and HCN4 channels (the 2 cardiac isoforms present in ventricles) expressed in HEK293 cells and by If in rat ventricular myocytes. We observed Ca2+ influx when HCN/ If channels were activated. Ca2+ influx was increased with stronger hyperpolarization or longer pulse duration. Cesium, an If channel blocker, inhibited If and Ca2+ influx at the same time. Quantitative analysis revealed that Ca2+ flux contributed to ∼0.5% of current produced by the HCN2 channel or If. The associated increase in Ca2+ influx was also observed in spontaneously hypertensive rat (SHR) myocytes in which If current density is higher than that of normotensive rat ventricle. In the absence of EGTA (a Ca2+ chelator), preactivation of If channels significantly reduced the action potential duration, and the effect was blocked by another selective If channel blocker, ZD-7288. In the presence of EGTA, however, preactivation of If channels had no effects on action potential duration. Our data extend our previous discovery of Ca2+ influx in Ih channels in neurons to If channels in cardiac myocytes.

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Developmental changes of action potential configuration and I(to) in canine epicardium

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.6.h2513 ◽

1995 ◽

Vol 268 (6) ◽

pp. H2513-H2521 ◽

Cited By ~ 5

Author(s):

L. M. Pacioretty ◽

R. F. Gilmour

Keyword(s):

Action Potential ◽

Time Constant ◽

Action Potential Duration ◽

Phase 1 ◽

Outward Current ◽

Ionic Currents ◽

Developmental Changes ◽

Transient Outward Current ◽

Rapid Phase ◽

Action Potential Configuration

Developmental changes of the transient outward current (I(to)) and action potential configuration were determined in canine epicardium ranging in age from fetal to 60 wk. The contributions of I(to) to rapid initial repolarization and to terminal repolarization were estimated by measuring the amplitude of phase 1 of the action potential and action potential duration, respectively. Phase 1 amplitude decreased progressively from fetal to 40 wk and remained constant thereafter. Action potential duration decreased from fetal to 2 wk, increased to 20 wk, and tended to decrease thereafter. Peak I(to) at +40 mV increased progressively from 2 to 60 wk. However, I(to) density was less at 2-10 wk than at 20-60 wk. The time constant of decay of I(to) increased with age from 2 to 60 wk, whereas the steady-state voltage dependence of inactivation did not vary with age. The time constant for the initial rapid phase of recovery from inactivation decreased from 2 to 10 wk and remained constant thereafter. The time constant for the more slowly evolving phase did not vary with age. The observation that the age-dependent reduction in phase 1 amplitude did not necessarily coincide with significant increases in I(to) density suggests that maturation of other ionic currents or transport mechanisms may contribute to developmental alterations of phase 1 repolarization.

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