Amount and Turnover of Calcium Entering the Cells of Ventricular Myocardium of Guinea Pig Heart in a Single Excitation

Activation-dependent cumulative depletions of extracellular free calcium in guinea pig atrium measured with antipyrylazo III and tetramethylmurexide.

“…The maximal depletions found in the present study with 2 to 7 beats would be in the range of calcium influx values suggested by Lewartowski et al (1982) for single beats in guinea pig ventricle under their control conditions. The present results suggest, therefore, that an influx of such magnitude may be possible, although not necessarily physiological.…”

“…Isenberg and Kloekner (1982) have shown in single cardiac cells that slow calcium inward current may be many times larger than values derived from multicellular preparations. Lewartowski et al (1982) have presented calcium flux data from a quiescent Langendorff preparation of guinea pig heart indicating a net calcium influx of more than 100 ^mol per kg wet weight with single 'rested state contractions ' (Koch-Weser and Blinks, 1963) in the presence of 1.8 mM extracellular calcium, an order of magnitude greater influx than generally accepted. Furthermore, most of the calcium taken up at one beat can apparently be released to the extracellular space at a single subsequent beat.…”

“…Cumulative depletion responses are also inhibited by 10 mM caffeine, whereby contraction and corresponding motion artifacts are increased at post-rest stimulation. (Circ Res 53: 779-793, 1983) TWO METHODS have been used most widely to attempt to quantify the magnitude and characteristics of transsarcolemmal calcium movements in intact cardiac muscle: radioisotope flux measurements (Winegrad and Shanes, 1962;Grossman andFurchgott, 1964a, 1964b;Langer and Brady, 1968;Niedergerke et al, 1969;Shine et al, 1971;Hunter et al, 1981;Lewartowski et al, 1982) and voltage clamp analysis (Beeler and Reuter, 1970;New and Trautwein, 1972;Isenberg and Kloekner, 1982). The former approach is not only limited temporally by the rate of calcium exchange with extracellular spaces, but also by the uncertainty of cellular identification of flux components (Langer et al, 1979;Barry and Smith, 1982).…”

“…Particularly the work of Lewartowski et al (1982), if correct, would challenge the most widely considered concepts of excitation-contraction coupling in cardiac muscle (Bassingthwaighte and Reuter, 1972;Morad and Goldman, 1973;Kaufmann et al, 1974;Reuter, 1974;Allen et al, 1976;Edman and Johannsson, 1976;Fabiato and Fabiato, 1979;Langer, 1980). The characteristics of these calcium movements (possibly large calcium influx, uptake by an intracellular store, and release to the extracellular space at a subsequent beat) correspond strikingly to those expected from a refined version (Mensing, 1979) of Langer's (1974) one-way model of calcium movements in mammalian heart.…”

Transsarcolemmal calcium movements in arterially perfused rabbit right ventricle measured with extracellular calcium-sensitive dyes.

“…These results demonstrate that most of the 'activator pool' of cellular calcium can turn over to the extracellular space during a single contraction cycle in rabbit myocardium, and suggest that, in mammalian myocardium, diastolic calcium efflux may be quantitatively negligible in relation to efflux during excitation-contraction coupling. (Circ Res 54: 461-467, 1984) RECENT studies by four different techniques would indicate that calcium influx at activation in cardiac muscle can be larger than widely accepted in the past years: first, voltage clamp analysis of calcium currents in myocytes (Isenberg and Kloeckner, 1982), which presumably reflects a high conductivity of single channels as found in patch clamp analysis (Reuter et al, 1982); second, isotope flux measurements of calcium movements at single beats (Lewartowski et al, 1982); third, measurement of activation-dependent extracellular calcium depletions with calcium-sensitive microelectrodes (Dresdner et al, 1982;Bers, 1983); and fourth, measurement of activation-dependent extracellular calcium depletions with calcium-sensitive absorption dyes (Hilgemann et al, 1983).…”