Ionic mechanism of morphological changes of cultured myocardial cells on successive incubation in media without and with Ca2+

Calcium, sodium, and the calcium paradox.

“…10), together with whatever Ca ++ is mobilized from the intracellular stores (Lee and Dhalla, 1976;Alto and Dhalla, 1981), is still sufficient to trigger such a contracrure, but after a slight delay. The delay in myoglobin release in the verapamil-treated group (Table 3) supports this concept, as does the persistent protective effect reported by Goshima et al (1980) for verapamil, because the second phase of Ca ++ entry would be absent if myocytes were being used.…”

“…In an earlier study, Goshima et al (1980) noted that preloading isolated myocytes with Na + accelerates Ca ++ uptake when Ca ++ is readmitted after a short period of Ca ++ depletion. Although our results substantiate their findings, there are several important differences between the two studies.…”

“…Although our results substantiate their findings, there are several important differences between the two studies. Whereas we used intact adult rat hearts at 37°C, Goshima et al (1980) used isolated myocytes prepared from fetal mouse hearts, and they carried out their experiments at 25°C. The Ca ++ paradox is age-(Chizzonite and Zak, 1981;Frank and Rich, 1983) and temperature-sensitive (Holland and Olson, 1975;Alto and Dhalla, 1979;Boink et al, 1980;Langer, 1982, Baker et al, 1983).…”

“…Therefore, unless a membrane defect, induced by Ca ++ -free perfusion, which renders the membrane freely permeable to Ca ++ is lost or concealed when the vesicles are isolated, it is difficult to account for the gain in Ca ++ simply in terms of an enhanced passive inward permeability with respect to Ca ++ . It is equally difficult to account for it solely in terms of an enhanced entry of Ca ++ in exchange for Na + , because, although intracellular Na + rises during Ca ++ -free perfusion (Goshima et al, 1980;Nayler et al, 1983aNayler et al, , 1983b, and although the Na + :Ca ++ exchange mechanism survives the paradox (Nayler et al, 1983a), the gain in Ca ++ that occurs upon repletion after 10 minutes of Ca ++ -free perfusion correlates poorly with cell Na + at the start of repletion (Nayler et al, 1983a). Neither can the Ca ++ repletion-induced gain in Ca ++ be accounted for simply in terms of an enhanced entry of Ca ++ through the voltage-activated slow channels, because, although verapamil may slightly reduce (but not abolish) enzyme and protein leakage (Hearse et al, 1980;Baker et al, 1983), it does not attenuate the gain in Ca ++ caused by 10 minutes of repletion after 10 minutes of Ca ++ -free perfusion .…”

Calcium paradox in guinea‐pig ventricular myocytes

“…This gained support from the finding that cellular enzymes were not released from isolated myocytes on Ca2' repletion (Piper, Spahr, Hutter & Spieckermann, 1985) and from the failure of Frank, Brady, Farnsworth & Mottino (1986) to detect structural changes in isolated myocytes after 15 min Ca2+ depletion followed by Ca2' repletion. The second explanation suggests that damage to the cell membrane results from other effects of the Ca2+ overload, such as the activation of proteases or phospholipases, and has received support from several workers (Goshima, Wakabayashi & Masuda, 1980;Persad, Vrbanova, Meij, Panagia & Dhalla, 1993;Suleiman, Minezaki, Ban & Chapman, 1994b) who have studied loading of the cells with Na+ and Ca2+, ultrastructural changes and the electrical measurements of the integrity of the sarcolemma. Changes were reported that were similar to those originally described for multicellular preparations (Yates & Dhalla, 1975;Alto & Dhalla, 1979 resulted because different methods of preparation of the isolated myocytes have been used on different species while the exact means used to provoke the Ca2+ overload has also varied.…”