Effects of thyroid hormone on the action potential and membrane currents of guinea pig ventricular myocytes

Binah, Ofer; Rubinstein, I.; Gilat, Eran

doi:10.1007/bf00584774

Cited by 65 publications

(25 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…He suggested that calcium antagonistic effects of amiodarone may play a dominant role in suppressing drug-induced early afterdepolarizations. A similar protective effect was discussed in hypothyroidism-induced QT prolongation [15,62]. Electrophysiologic changes after long-term amiodarone therapy are very similar to those during hypothyroidism, which argues for a similar cellular mode of action [208].…”

Section: Characteristics Of Proarrhythmia After Drug-lnduced Qt Prolomentioning

confidence: 74%

QT-Interval prolonging drugs: Mechanisms and clinical relevance of their arrhythmogenic hazards

Zehender

Hohnloser

Just

1991

Cardiovasc Drug Ther

View full text Add to dashboard Cite

The antiarrhythmic principle of drug-induced QT-interval prolongation is well known. However, with the widespread use of the presently known and new Class III antiarrhythmic agents under investigation, and the growing number of agents not primarily designed as antiarrhythmic drugs that potentially cause QT prolongation, we have also become aware of the proarrhythmic hazards associated with many of these agents. The proarrhythmic risk differs markedly from one agent to another and interferes with many individual clinical variables (e.g., hypokalemia, sinus bradycardia). This paper summarizes the present data on the proarrhythmic risk of drug-induced QT prolongation, including the value and problems of the rate-corrected QT interval, the mechanisms involved in the genesis of proarrhythmia, and the clinical cofactors that facilitate the occurrence of proarrhythmic events. In addition, an extensive database provides information on the known proarrhythmic risk of all currently used QT-prolonging agents.

show abstract

Section: Characteristics Of Proarrhythmia After Drug-lnduced Qt Prolomentioning

confidence: 74%

QT-Interval prolonging drugs: Mechanisms and clinical relevance of their arrhythmogenic hazards

Zehender

Hohnloser

Just

1991

Cardiovasc Drug Ther

View full text Add to dashboard Cite

show abstract

“…Changes in electrical activity in hyperthyroid conditions have been well defined (Morkin et al 1983;Sharp et al 1985;Binah, Rubinstein & Gilat, 1987). Studies investigating underlying ionic mechanism, using voltage clamp methods, have concentrated on calcium currents.…”

Section: Introductionmentioning

confidence: 99%

Hyperthyroidism selectively modified a transient potassium current in rabbit ventricular and atrial myocytes.

Shimoni

Banno

Clark

1992

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. Transient outward potassium currents (It) were compared in single cardiac myocytes obtained from normal and hyperthyroid rabbits. Currents were recorded using the suction electrode whole-cell voltage clamp technique.2. In ventricular myocytes from hyperthyroid animals (at 22 TC and a stimulation rate of 0-2 Hz), It was 4-to 5-fold larger than in normal myocytes, in a potential range of -20 to + 60 mV. As in normal myocytes, It in hyperthyroid myocytes was calcium insensitive, and was more than 90 % suppressed by 2 mm 4-aminopyridine.3. The increase in It was observed over a wide range of stimulation rates, even at rates sufficiently slow to enable complete reactivation of the It channels. However, there was a major change in the rate dependence of It in hyperthyroid myocytes, with significant It current still present at rates (e.g. 1-2 Hz) at which it is normally completely suppressed.4. The augmentation of It in the hyperthyroid myocytes could not be accounted for by changes in the voltage dependence or the kinetics of channel activation or inactivation. There was no change in the reversal potential of It, implying no change in the selectivity of the channel.5. Single-channel activity was recorded using the cell-attached mode of recording. In myocytes from hyperthyroid rabbit we observed the following: (a) active patches (often containing two channels) were obtained more frequently in comparison to control; (b) the unitary conductance of the channel was the same; (c) single-channel openings persisted at high stimulation rates.6. In contrast to hyperthyroid ventricular cells, It in atrial cells from the same hearts was not substantially changed.7. The rate dependence of It in atrial cells was also unaffected by hyperthyroidism, in contrast to the large changes observed in ventricular cells. Thus, in atrial cells from hyperthyroid hearts the current was totally suppressed at rates of 1-2 Hz, as in euthyroid conditions.

show abstract

“…Compelling data supporting biological activities of THs that are independent of nuclear effects came from early studies of erythrocytes (3,39,62), of myocardial membrane calciumATPase activity (212), on the rapid-onset of T3 effects on sodium and calcium currents in cardiac myocytes (18,35,222,235,236,257), and on contractile responses of vascular smooth muscle cells and resistance arteries (176,178,197). Sites of action responsible for these effects have been identified in the plasma membrane and cytosol [reviewed in (30)].…”

Section: Non-nuclear Actions Of Thsmentioning

confidence: 98%

“…In chronic thyroid disease, changes in cardiac electrophysiology have been well documented (18,131,225,280), and can be attributed to altered expression of genes including sodium-potassium ATPase (133,271) and voltage-activated K+ channels including Kv4.2, Kv4.3, and Kv1.5 (180,224,265). However, electrophysiological studies of isolated atrial and ventricular myocytes have clearly shown that pacemaker activity, repolarizing currents, and intracellular calcium can be altered rapidly by T3 independent of transcriptional changes (216,235,236).…”

Section: Th Effects On Intracellular Calcium and Ion Currentsmentioning

confidence: 99%

Thyroid Hormone and Cardioprotection

Gerdes

Ojamaa

2016

Comprehensive Physiology

View full text Add to dashboard Cite

The heart is a major target of thyroid hormones, with maintenance of euthyroid hormone balance critical for proper function. In particular, chronic low thyroid function can eventually lead to dilated heart failure with impaired coronary blood flow. New evidence also suggests that heart diseases trigger a reduction in cardiac tissue thyroid hormone levels, a condition that may not be detectible using serum hormone assays. Many animal and clinical studies have demonstrated a high prevalence of low thyroid function in heart diseases with worse outcomes from this condition. Animal and human studies have also demonstrated many benefits from thyroid hormone treatment of heart diseases, particularly heart failure. Nonetheless, this potential treatment has not yet translated to patients due to a number of important concerns. The most serious concern involves the potential of accidental overdose leading to increased arrhythmias and sudden death. Several important clinical studies, which actually used excessive doses of thyroid hormone analogs, have played a major role in convincing the medical community that thyroid hormones are simply too dangerous to be considered for treatment in cardiac patients. Nonetheless, this issue has not gone away due primarily to overwhelmingly positive evidence for treatment benefits and a new understanding of the cellular and molecular mechanisms underlying those benefits. This review will first discuss the clinical evidence for the use of thyroid hormones as a cardioprotective agent and then provide an overview of the cellular and molecular mechanisms underlying beneficial changes from thyroid hormone treatment of heart diseases. © 2016 American Physiological Society. Compr Physiol 6:1199-1219, 2016.

show abstract

Effects of thyroid hormone on the action potential and membrane currents of guinea pig ventricular myocytes

Cited by 65 publications

References 11 publications

QT-Interval prolonging drugs: Mechanisms and clinical relevance of their arrhythmogenic hazards

QT-Interval prolonging drugs: Mechanisms and clinical relevance of their arrhythmogenic hazards

Hyperthyroidism selectively modified a transient potassium current in rabbit ventricular and atrial myocytes.

Thyroid Hormone and Cardioprotection

Contact Info

Product

Resources

About