Influence of thyroid hormone levels on the electrical and mechanical properties of rabbit papillary muscle

Sharp, Nina A.; Neel, Darcy S.; Parson, Rodney L.

doi:10.1016/s0022-2828(85)80015-8

Cited by 64 publications

(31 citation statements)

References 35 publications

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“…1A. This configuration resembles the action potentials recorded by Sharp et al (1985), as well as by Litovski & Antzelevitch (1988) in canine epicardial tissue, and strongly suggests a major role for the transient outward potassium current It (as proposed by Sharp et al 1985). Further evidence for a role of this current in producing these complex action potential configurations was obtained by applying 4-aminopyridine (4-AP) or increasing the rate of stimulation.…”

Section: Action Potentialssupporting

confidence: 72%

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

Shimoni

Banno

Clark

1992

The Journal of Physiology

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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.

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Section: Action Potentialssupporting

confidence: 72%

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

Shimoni

Banno

Clark

1992

The Journal of Physiology

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“…Hyperthyroidism has been found to be associated with decreased as well as increased repolarization times. In animal studies (Johnson et al 1973, Sharp et al 1985, Binah et al 1987, Gomberg-Maitland & Frishman 1998) and in one human study (Dorr et al 2006), decreased repolarization times have been found, however, in several small human studies (Linder 1955, Fisher 1982, Colzani et al 2001, Owecki et al 2006 and in an animal study (Johansson et al 2002), QTc prolongation has been reported. In a prospective study comparing 16 patients with Graves' disease with a matched reference group, the 24-h average QTc in the Graves' patients was significantly prolonged and returned to normal after treatment of thyrotoxicosis.…”

Section: Discussionmentioning

confidence: 97%

“…In hyperthyroidism, the situation is more controversial, since prolonged and shortened QTc intervals both have been reported (Linder 1955, Johnson et al 1973, Fisher 1982, Sharp et al 1985, Binah et al 1987, Gomberg-Maitland & Frishman 1998, Colzani et al 2001, Dorr et al 2006, Owecki et al 2006. Decreased repolarization times have been reported in several animal studies (Johnson et al 1973, Sharp et al 1985, Binah et al 1987, Gomberg-Maitland & Frishman 1998 and in one human study (Dorr et al 2006) and at the same time, QTc prolongation has been reported in patients with hyperthyroidism (Linder 1955, Fisher 1982, Colzani et al 2001, Owecki et al 2006. A potential explanation for an association with prolongation of the QTc interval is an increased activity of cardiac Na C /K C ATPase in thyroid hormone excess, leading to increased intracellular K C with subsequent membrane hyperpolarization and an increase in QTc duration (Polikar et al 1993, Colzani et al 2001.…”

Section: Introductionmentioning

confidence: 99%

High free thyroxine levels are associated with QTc prolongation in males

Noord¹,

Deure²,

Sturkenboom³

et al. 2008

Journal of Endocrinology

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The literature on the effect of excess thyroid hormone on ventricular repolarization is controversial. To study whether free thyroxine (T 4 ) and TSH are associated with QTc prolongation we conducted population-based cohort study. This study was conducted as part of the Rotterdam Study and included 365 men and 574 women aged 55 years and older with an electrocardiogram, who were randomly sampled for the assessment of thyroid status (free T 4 /TSH) at baseline, after exclusion of participants with hypothyroidism, use of antithyroid drugs, thyroid hormones or digoxin, left ventricular hypertrophy, and left and right bundle branch block. Endpoints were the length of the QTc interval and risk of borderline QTc prolongation. The associations were examined by means of linear and logistic regression analysis, adjusted for age and gender, diabetes mellitus, myocardial infarction, hypertension, and heart failure. Overall, there was no significant association between TSH and QTc interval (0 . 8 ms (95% confidence interval (CI) K3 . 5, 5 . 2) in the first quintile compared with the fifth quintile). Subjects in the fifth quintile of free T 4 did not have an increased QTc interval (3 . 2 ms (95% CI K1 . 1, 7 . 6)); stratification on gender showed an increment of 10 . 9 ms (95% CI 3 . 4, 18 . 3) in the fifth quintile in men and 1 . 1 ms (95% CI K4 . 2, 6 . 3) in the fifth quintile of free T 4 in women. When compared with subjects in the first quintile, male subjects in the fifth quintile of free T 4 had a significantly increased risk of a borderline QTc interval and QTc prolongation (odds ratio 2 . 40 (95% CI 1 . 20, 4 . 80)). High levels of free T 4 are associated with substantial QTc prolongation in men of up to 10 ms. The fact that free T 4 is also associated with a significantly increased risk of borderline and prolonged QTc values with its risk of sudden cardiac death, endorses the clinical importance of our findings.

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“…(Circulation Research 1993;73:301-313) KEY WoRDs * thyroid hormone * triiodothyroacetic acid * sodium currents * modal gating modulation F or some time, thyroid hormone has been known to alter cardiac electrophysiological properties. Chronic hyperthyroidism shortens the action potential duration",2 and increases the whole-cell Ca 2 and K' currents.3 These effects seem to be independent of the modulation of the autonomic nervous system by hyperthyroidism.14 Thyroid hormone's action generally is thought to require protein synthesis. However, recent evidence suggests that 3,5,3'-triiodo-L-thyronine (T3) has specific cardiac membrane binding sites and can acutely influence the sarcolemmal Ca2-ATPase,5 adenylate cyclase,6 the number of -and a-adrenergic receptors,7 and 2-deoxyglucose transport.8 Studies on plasma membrane T3 receptors and the extranuclear effects of T3 were reviewed recently by Segal.9 In contrast to the abbreviation of action potential duration in chronic hyperthyroidism,1'2 acute exposure to T3 causes a significant prolongation of action potential duration in isolated neonatal rat myocytes.10 Studies using whole-cell voltage clamp recently revealed that 5 nM T3 increases the amplitude of the Na+ current and slows inactivation of the macroscopic current.10"11 The present experiments were undertaken to characterize the acute effects of physiological concentrations of T3 on Na+ channels at the single-channel level.…”

mentioning

confidence: 99%

Bursting of cardiac sodium channels after acute exposure to 3,5,3'-triiodo-L-thyronine.

Dudley

Baumgarten

1993

Circulation Research

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Physiological concentrations of 3,5,3'-triiodo-L-thyronine (T3) acutely increased burst-mode gating of Na+ channels in rabbit ventricular myocytes. Bursting was measured as the ratio of long events to the total number of events multiplied by 100 (%LE); a long event was defined as a set of openings or a single opening with a total duration greater than or equal to five times the control mean open time (MOT) for cell-attached patches. In the cell-attached configuration, adding either 5 or 50 nM T3 to the pipette increased the %LE. %LE had a biphasic voltage dependence and peaked at -50 mV, although the largest percentage change from control occurred between -30 and -40 mV. Neither unitary conductance nor the overall MOT was altered by T3-induced bursting. However, the MOT of openings within bursts increased, implying a kinetically distinct mode of channel gating during bursts. Long events sometimes were grouped into runs, but the more usual pattern suggested that modal shifts occurred in = 1 second. Similar behavior was observed with triiodothyroacetic acid, a T3 analogue that does not elicit protein synthesis. To investigate involvement of soluble second messengers, cell-attached recordings were made with and without T3 in the bath. Placed outside the pipette, 50 and 100 nM T3 failed to alter MOT, unitary current, or %LE. Na+ channel gating also was unaffected by patch excision and by exposing the cytoplasmic face of inside-out patches to 50 nM T3. Nevertheless, excision to the inside-out configuration with 5 nM T3 in the pipette dramatically increased the %LE and lengthened MOT. These results suggest that T3 induced Na+ channel bursting by an extranuclear mechanism that requires proximity of T3 to the extracellular face of the Na+ channel. Furthermore, T3 was not membrane permeant on the time scale of these experiments. Na+ channel bursting may contribute to the propensity for arrhythmias in hyperthyroidism and to the positive inotropic effect of acute T3 administration in the stunned and ischemic myocardium. (Circulation Research 1993;73:301-313) KEY WoRDs * thyroid hormone * triiodothyroacetic acid * sodium currents * modal gating modulation F or some time, thyroid hormone has been known to alter cardiac electrophysiological properties. Chronic hyperthyroidism shortens the action potential duration",2 and increases the whole-cell Ca 2 and K' currents.3 These effects seem to be independent of the modulation of the autonomic nervous system by hyperthyroidism.14 Thyroid hormone's action generally is thought to require protein synthesis. However, recent evidence suggests that 3,5,3'-triiodo-L-thyronine (T3) has specific cardiac membrane binding sites and can acutely influence the sarcolemmal Ca2-ATPase,5 adenylate cyclase,6 the number of -and a-adrenergic receptors,7 and 2-deoxyglucose transport.8 Studies on plasma membrane T3 receptors and the extranuclear effects of T3 were reviewed recently by Segal.9In contrast to the abbreviation of action potential duration in chronic hyperthyroidism,1'2 acute exposure to...

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Influence of thyroid hormone levels on the electrical and mechanical properties of rabbit papillary muscle

Cited by 64 publications

References 35 publications

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

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

High free thyroxine levels are associated with QTc prolongation in males

Bursting of cardiac sodium channels after acute exposure to 3,5,3'-triiodo-L-thyronine.

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