INTRACELLULAR CITRATE INDUCES REGENERATIVE CALCIUM-RELEASE FROM SARCOPLASMIC-RETICULUM IN GUINEA-PIG ATRIAL MYOCYTES

Ca2+ release from the sarcoplasmic reticulum was studied in voltage-cl amped guinea-pig atrial myocytes. Cells were dialysed with a pipette s olution containing the Ca2+ indicator 1-[2-amino-5-(6-carboxyindol-2-y l) phenoxy]-2-(2'-amino-5'-methylphenoxy) ethane-N,N,N',N'-tetraacetic acid] (Indo-1, 100 mu M) and as main anion either chloride or the low -affinity Ca2+ buffer citrate. Intracellular Ca2+ transients (Ca-i tra nsients) were elicited by depolarizations from a holding potential of -50 mV. In chloride-dialysed cells, Ca-i transients showed a bell-shap ed dependence on the amplitude of the depolarizing pulse. In citrate-d ialysed cells, membrane depolarizations were associated with a small r ise in [Ca2+](i). These small changes in [Ca2+](i) were either followe d by a large Ca-i transient or failed to induce large changes in [Ca2](i). The peak amplitude of the large Ca-i transient did not vary with the amplitude of the depolarizing pulse. These results demonstrate th at in the presence of intracellular chloride, Ca2+ release in atrial c ells is a graded process triggered by Ca2+ influx. Using citrate as th e main intracellular anoin, Ca2+ release triggered by Ca2+ entry was n o longer graded but occurred in a regenerative manner. The results are discussed in terms of two models in which citrate, affects the spatia l distribution of [Ca2+](i) or the loading state of the sarcoplasmic r eticulum.