Factors influencing free intracellular calcium concentration in quiescent ferret ventricular muscle.

The photoprotein aequorin was injected into cells of ferret papillary muscles to monitor the resting intracellular free Ca concentration ( Ca2+i). Increasing the external Ca concentration ( Ca2+o) increased both resting Ca2+i and resting tension. The tension and Ca2+i both rose to a peak and then declined to a steady-state level which was higher than the control. Qualitatively similar, but larger, effects were observed if Ca2+i was first elevated with strophanthidin. The increase of Ca2+i was accompanied by the development of spontaneous oscillations of Ca2+i. When a steady level of Ca2+i had been reached in high Ca2+o, Ca2+o was reduced back to the control level for a brief period. A subsequent increase of Ca2+o produced a rise of Ca2+i to the same steady level as that previously found in the high Ca2+o but the initial peak and subsequent decline were absent. It is suggested that the decline of Ca2+i from the initial peak is mediated by a fall of intracellular Na concentration ( Na+i) limiting Ca entry on a Na-Ca exchange. Increasing external K concentration ( K+o) from 5 to 30 mmol/l had no detectable effect on Ca2+i under control conditions. However, if Ca2+i was first increased either by applying strophanthidin or by increasing Ca2+o, increasing K+o produced a transient rise of Ca2+i and tension. This rise was unaffected by D600. It is suggested that the secondary decline of Ca2+i after the initial rise may, again, be produced by a fall of Na+i acting on an Na-Ca exchange. Acidification produced by increasing CO2 had no detectable effect on Ca2+i under control conditions. However, if Ca2+i was increased by strophanthidin, acidification produced a rise of Ca2+i. This rise of Ca2+i was partly transient even when the intracellular acidification was presumably maintained (raising CO2 at constant HCO3-). Acidification in Na-free solutions had qualitatively similar effects to those in Na-containing solutions. In Na-free solutions (Na replaced by K) the Ca2+i could be maintained at a low level for at least several hours. Increases of Ca2+o in Na-free solutions led to a decrease of Ca2+i, and similarly decreasing Ca2+o led to an increase in Ca2+i. These anomalous effects of Ca2+o on Ca2+i could be abolished by Mn ions or D600. It is suggested that changes in Ca2+o may have reciprocal effects on Ca permeability and hence on Ca2+i. The application of the mitochondrial uncoupler FCCP in Na-free solutions led to an increase of resting tension followed, after a substantial delay, by an increase of Ca2+i.(ABSTRACT TRUNCATED AT 400 WORDS)