Mechanochemistry of cardiac muscle

Skelton, C. Lynn; Pool, Peter E.; Seagren, Shirley C.; Braunwald, Eugene

doi:10.1172/jci106514

Cited by 26 publications

(2 citation statements)

References 29 publications

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“…A variety of processes are candidates for mediating roles in Na'-independent thermogenesis. Skelton et al (37) proposed that thyroid hormone increases energy utilization in the cardiac contraction-relaxation cycle. Another candidate is active Ca"+ transport in sarcoplasmic reticulum.…”

Section: Discussionmentioning

confidence: 99%

Thyroid thermogenesis. Relationships between Na+-dependent respiration and Na+ + K+-adenosine triphosphatase activity in rat skeletal muscle.

Asano¹,

Liberman²,

Edelman³

1976

J. Clin. Invest.

155

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A B S T R A C T The effect of thyroid status on Qo2, Qo2-(t) and NaK-ATPase activity was examined in rat skeletal muscle. Qo2(t) (i.e. Na'-transport-dependent respiration) was estimated with ouabain or Na'-free media supplemented with K+. In contrast to the effects of ouabain on ion composition, intracellular K+ was maintained at about 125 meq/liter, and intracellular Na' was almost nil in the Na+-free media. The estimates of Qo2 (t) were independent of the considerable differences in tissue ion concentrations. The increase in Qo2(t) accounted for 47% of the increase in QO2 in the transition from the hypothyroid to the euthyroid state and 84% of the increase in the transition from the euthyroid to the hyperthyroid state. Surgical thyroidectomy lowered NaK-ATPase activity of the microsomal fraction (expressed per milligram protein) 32%; injections of triiodothyronine (Ts) increased this activity 75% in initially hypothyroid rats and 26% in initially euthyroid rats. Thyroidectomy was attended by significant falls in serum Ca and P1 concentrations. Administration of Ts resulted in further declines in serum Ca and marked in- creases in serum P1 concentrations. Similar effects were seen in "TI-treated rats, but the magnitude of the declines in serum Ca were less. The effects of T3 on Qos, Qo2(t), and NaK-ATPase activity of skeletal muscle were indistinguishable in the "mI-ablated and surgically thyroidectomized rats.

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Section: Discussionmentioning

confidence: 99%

Thyroid thermogenesis. Relationships between Na+-dependent respiration and Na+ + K+-adenosine triphosphatase activity in rat skeletal muscle.

Asano¹,

Liberman²,

Edelman³

1976

J. Clin. Invest.

155

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“…Formerly it was thought that increased sensitivity of the sympathetic nervous system mediated by thyroxine could explain the responses ( 1, 2 ) . However, this hormone also has a direct myocardial (cellular) effect which could be responsible for the altered contractility (3,4,5,6). Indeed, both of these mechanisms may operate in vivo and account for the altered chronotropic and inotropic responses of hyperthyroid hearts.…”

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confidence: 99%

Sensitivity of Hyperthyroid Cat Myocardium to Decreased Extracellular Calcium

Dempsey

Kent

McCallum

et al. 1972

Experimental Biology and Medicine

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The mechanism of the observed alteration in the contractile state of the heart observed in clinical hyperthyroidism has remained a difficult mechanism to delineate. Formerly it was thought that increased sensitivity of the sympathetic nervous system mediated by thyroxine could explain the responses ( 1, 2 ) . However, this hormone also has a direct myocardial (cellular) effect which could be responsible for the altered contractility (3, 4, 5, 6). Indeed, both of these mechanisms may operate in vivo and account for the altered chronotropic and inotropic responses of hyperthyroid hearts. Since in vitro experiments have revealed increased contractility of hyperthyroid cat myocardium, the purpose of the present experiment was to examine the responses of hyperthyroid cat myocardium to calcium, the key element in the excitation-contraction coupling mechanism.I n work previously done in our laboratory, we have demonstrated that ouabain is capable of producing negative inotropic responses in isolated cat papillary muscle exposed to extracellular calcium concentrations less than 0.6 mM ( 7 ) . The responses to ouabain at low extracellular calcium concentrations of hyperthyroid cat myocardium, however, appeared to be more pronounced than controls, i.e., greater depression of contractility.The purpose of the present experiments was to examine the sensitivity of two different cellular processes of hyperthyriod myocardium to extracellular calcium concentrations. The developed isometric tension and its first derivative and the transmembrane action potential were the measured responses.Materials and Met hods. Right ventricular papillary muscles were removed from 56 control cats and from 30 cats which had received 1-thyroxine, 0.75 mg/kg/day for 21 days. One end of the muscle was held in a fixed position and the other end attached to a force displacement transducer for tension measurement. Isometric tension was measured at L,,,,, and the first derivative of the tension tracing (dT/dt) was monitored online by means of an active differentiator with a time constant of 1 msec. A horizontal, 25 ml lucite flow-through bath was perfused with Krebs solution at 25" and equilibrated with 95% 0,-5c/o COa. Muscles were stimulated to contract isometrically a t 12/min by means of fine platinum electrodes placed in close proximity on either side of the muscle base at a voltage 5% to 10% above threshold. Transmembrane action potentials (TAP) were recorded by means of standard 3M KC1-filled glass micro-electrodes mounted in a right-angle assembly with signal amplification by a Bak standard electrometer and a Tektronix model 502 dual beam oscilloscope.Total duration of the TAP as well as times for 50% repolarization were the characteristics examined. Tension, dT/dt and transmembrane action potentials were recorded on a direct writing oscillograph as well as on a multichannel Hewlett-Packard 395 5 tape system.Since Ca++ concentration was critical in these experiments, great care was taken in the preparation of the low Ca++ solutions. Solutions wer...

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