The effect of oxygen free radicals on calcium current and dihydropyridine binding sites in guinea-pig ventricular myocytes

We examined the effects of oxygen free radicals (OFRs) on action potentials and membrane currents of guinea pig ventricular myocytes. OFRs produced biphasic changes in the action potential duration, initial lengthening (30 s after exposure to OFRs) and subsequent shortening (within 5 min). In voltage-clamp experiments, OFRs suppressed the L-type calcium current, the delayed rectifier K+ current, and the inward rectifier K+ current. In addition, OFRs increased the time-independent outward current (I(term)) at potentials greater than -30 mV. The increases in I(term) reflected activation of the ATP-sensitive K+ (KATP) channels, as glibenclamide (1 microM) blocked this current. In inside-out patches, OFRs significantly increased the open probability of the channel at a relatively narrow range of ATP concentrations (0.2–2 mM), and this effect was enhanced in the presence of ADP (0.1 mM) and abolished in the presence of either free radical scavengers or gliben-clamide. These findings are compatible with the notion that OFRs activate KATP channels by modulating ATP binding sites of the KATP channels, without affecting ADP binding or glibenclamide binding sites.

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Effects of free Radicals on Calcium Currents in Single Guinea-Pig Ventricular Myocytes

Clinical Science ◽

10.1042/cs084010p ◽

1993 ◽

Vol 84 (s28) ◽

pp. 10P-10P

Author(s):

F Lu ◽

JS Gill ◽

D Katritsis ◽

AJ Camm

Keyword(s):

Free Radicals ◽

Guinea Pig ◽

Ventricular Myocytes ◽

Calcium Currents

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The effect of ryanodine on calcium current in guinea pig ventricular myocytes is medicated by calcium

Journal of Molecular and Cellular Cardiology ◽

10.1016/0022-2828(91)91593-g ◽

1991 ◽

Vol 23 ◽

pp. S91

Author(s):

C BALKE

Keyword(s):

Guinea Pig ◽

Calcium Current ◽

Ventricular Myocytes

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Effect of Free Radicals on Excitation-Contraction Coupling in Isolated Rat and Guinea Pig Ventricular Myocytes

Excitation-Contraction Coupling in Skeletal, Cardiac, and Smooth Muscle - Advances in Experimental Medicine and Biology ◽

10.1007/978-1-4615-3362-7_28 ◽

1992 ◽

pp. 333-334

Author(s):

Magda Horackova ◽

Andrzej Beresewicz

Keyword(s):

Free Radicals ◽

Guinea Pig ◽

Ventricular Myocytes ◽

Excitation Contraction Coupling ◽

Contraction Coupling ◽

Isolated Rat

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Stimulation-dependent facilitation of the high threshold calcium current in guinea-pig ventricular myocytes.

The Journal of Physiology ◽

10.1113/jphysiol.1990.sp018233 ◽

1990 ◽

Vol 428 (1) ◽

pp. 653-671 ◽

Cited By ~ 62

Author(s):

A C Zygmunt ◽

J Maylie

Keyword(s):

Guinea Pig ◽

Calcium Current ◽

Ventricular Myocytes ◽

High Threshold

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Modification of cardiac adrenergic receptors by oxygen free radicals

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.260.3.h821 ◽

1991 ◽

Vol 260 (3) ◽

pp. H821-H826 ◽

Cited By ~ 3

Author(s):

M. Kaneko ◽

D. C. Chapman ◽

P. K. Ganguly ◽

R. E. Beamish ◽

N. S. Dhalla

Keyword(s):

Free Radicals ◽

Xanthine Oxidase ◽

Binding Sites ◽

Adrenergic Receptors ◽

Oxygen Free Radicals ◽

Beta Adrenergic Receptors ◽

Beta Adrenergic ◽

Alpha Adrenergic Receptors ◽

Cgp 12177 ◽

Number Of Binding Sites

To examine the effects of oxygen free radicals on alpha- and beta-adrenergic receptors, rat heart crude membranes were incubated with xanthine plus xanthine oxidase, H2O2, or H2O2 plus Fe2+. The assay of beta-adrenergic receptors involving [3H]dihydroalprenolol (DHA) binding revealed that the maximal number of binding sites (Bmax) and dissociation constant (Kd) were increased by xanthine plus xanthine oxidase. H2O2 increased the Kd value for [3H]DHA binding. When a hydrophilic ligand, [3H]CGP-12177, was used for the beta-adrenergic receptor assay, an increase in Kd value without any changes in Bmax value was evident on treating the membranes with xanthine plus xanthine oxidase. The assay of alpha-adrenergic receptors involving [3H]prazosin binding showed a decrease in the number of binding sites and an increase in Kd value only after a prolonged period of incubation. Both H2O2 and H2O2 plus Fe2+ increased the Kd value for [3H]prazosin without changes in Bmax. Changes in both alpha- and beta-adrenergic receptors similar to those with crude membranes were also seen by employing the purified heart sarcolemmal membranes. These data indicate that adrenergic receptors in the sarcolemmal membranes are modified by oxygen free radicals.

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