Sodium-calcium exchange in regulation of cardiac contractility. Evidence for an electrogenic, voltage-dependent mechanism.

4. The only scheme to fit all the experimental data satisfactorily is one which assumes an exchange of one Ca ion for three Na ions across the membrane. This scheme requires that the contractile system has an apparent binding constant for Ca2+, similar to that found with skinned cardiac muscle cells or isolated cardiac myofibrils. In intact muscle, when the [Na]1 is close to that measured experimentally, the model predicts that tension should vary with the [Ca]

Section: Discussionsupporting

confidence: 69%

The interaction of sodium and calcium ions at the cell membrane and the control of contractile strength in frog atrial muscle.

Chapman¹,

Tunstall²

1980

“…To test directly the effect of T3 on Ca2+ influx via Na+-Ca2+ exchange, Ca2+ uptake was determined in response to a step change to medium containing no Na+, which reverses the trans-sarcolemmal gradient for Na+ and promotes Ca2+ influx via Na+-Ca2+ exchange. The existence of Na+-sensitive Ca2+ flux has been well documented by many investigators in cardiac tissues and cultured heart cells (Glitsch, Reuter & Scholtz, 1970;Langer, Nudd & Ricchiuti, 1976;Fosset, DeBarry, Lenoir & Lazdunski, 1977;Horackova & Vassort, 1979;Reeves & Sutko, 1979;Pitts, 1979;Barry & Smith, 1982). In the presence of verapamil, Ca2+ uptake in response to exposure to Na+-free medium was significantly higher in cells grown in 10-8 M-T3 than without it, indicating that Ca2+ influx via Na+-Ca2+ exchange is also increased by thyroid hormone.…”

Section: Discussionmentioning

confidence: 86%

Effects of thyroid hormone on calcium handling in cultured chick ventricular cells.

Kim¹,

Smith²

1985

SUMMARY1. Mechanisms underlying thyroid hormone-induced changes in myocardial contractile state were investigated by studying the effects of triiodothyronine (T3) on Ca2+ fluxes across the sarcolemmal membrane and Ca2+ handling by the sarcoplasmic reticulum, using spontaneously contracting monolayers of cultured chick embryo ventricular cells.2. Cells were grown in serum-free medium containing either no T3 or 10-8 M-T3 for 48 h. At [Ca2+]. levels of 0-6 and 1-2 mm, the velocity of cell contraction was significantly greater in cells grown in 10-8 M-T3 than in its absence. At higher [Ca2+]0, no differences in the velocity of contraction were noted. 3. 45Ca2+ exchange kinetic studies showed a biexponential pattern with a rapid and a slow component of uptake in cells grown both with and without 10-8 M-T3. The rate of the rapid phase of uptake and total Ca2+ content were higher in cells grown in T3, with the increment in content ascribable to the rapidly exchangeable Ca2+ pool.4. Verapamil partially inhibited the T3-induced increase in the rapidly exchangeable pool. 45Ca2+ uptake in response to a step change to Na+-free medium in the presence of 1 ,/M-verapamil was significantly greater in cells grown in 10-8 M-T3 than in T3-free medium.5. Cells grown in T3 showed 20% greater beating rate than cells grown in its absence. A similar increase in beating rate achieved by lowering [K+]. from 4 0 to 3 0 mM or by electrical stimulation failed to affect the rate of 45Ca2+ uptake or the size of the rapidly exchangeable pool; pacing-induced increases in rate resulted in reduction rather than augmentation of contractile state.6. Ca2+ efflux rate was greater in cells grown in 10-8 M-T3 than in T3-free medium, whereas cells loaded with various levels of Ca2+ acutely by incubation at selected[Ca2+]0 levels had similar efflux rates. Replacement of Na+ by choline in the efflux medium resulted in elevated Ca2+ efflux rates in cells grown both with and without T3; however, it remained greater in cells grown in 10-8 M-T3 than in its absence.7. Caffeine (20 mM) in the efflux medium increased Ca2+ efflux to a greater degree in cells grown in T3 than without it. Caffeine also produced a greater tonic contraction in T3-treated cells than in cells grown in absence of T3 in Na+-and Ca2+-free medium.8. Cellular content of sarcoplasmic reticulum Ca2+-ATPase, as judged by maximal 5-2

“…7). As noted by Eisner & Lederer (1979), voltage-dependent tonic tension might be caused by modulation of an electrogenic Na-Ca exchange process (Horackova & Vassort, 1979) Fig. 8.…”

Section: Methodsmentioning

confidence: 83%

Voltage‐clamp studies of transient inward current and mechanical oscillations induced by ouabain in ferret papillary muscle

Karagueuzian

Katzung

1982

105

SUMMARY1. We studied the effects of a toxic concentration of ouabain on transmembrane electrical activity and on mechanical behaviour of right ventricular papillary muscles from ferrets in a single sucrose-gap using current clamp and voltage clamp.2. Ouabain (14-1-8 /M) induced oscillatory after-potentials and after-concentrations in current-clamp experiments. Voltage clamp showed that the oscillatory after-potential was caused by a transient inward current, similar to that in Purkinje fibres.3. The transient current had a sigmoidal dependence on the preceding (activating) voltage step VI, with a threshold around -13 mV and a plateau between + 10 and 20 mV. There was a decline in current amplitude for more positive clamps. When activated by a fixed VI voltage step, and measured at different repolarization levels V2, the transient current manifested an inverse dependence on V2 between -50 and -10 mV. No outward transient current could be detected. Total replacement of Na in the bathing medium by Tris or by sucrose abolished the transient current.4. Ouabain caused an increase of phasic (twitch) tension responses to voltage steps at all potentials without shifting the curve relating these variables on the voltage axis. The drug evoked an even greater increase in the tonic tension responses.5. After prolonged exposure, oscillatory mechanical responses were frequently recorded during positive voltage steps. Unlike the after-contraction, these mechanical fluctuations were not consistently damped and were not accompanied by detectable synchronous current fluctuations. Catecholamines and dibutyryl cyclic AMP markedly reduced the amplitude of the tonic contraction and the mechanical oscillations but increased their frequency. Caffeine had no effect on the tonic contraction amplitude but abolished the fluctuations.6. These results support the proposal that Ca is transiently released from the overloaded sarcoplasmic reticulum in ouabain-intoxicated muscle and may evoke oscillatory responses in nearby contractile fibrils. When these transient increases of sarcoplasmic free Ca are large enough, they may induce the transient transmembrane current described above.