title: Intracellular citrate induces regenerative calcium release from sarcoplasmic reticulum in guinea-pig atrial myocytes.
abstract: Ca2+ release from the sarcoplasmic reticulum was studied in voltage-clamped guinea-pig atrial myocytes. Cells were dialysed with a pipette solution containing the Ca2+ indicator 1- [2-amino-5-(6-carboxyindol-2-yl) phenoxy]-2-(2'-amino-5'-methylphenoxy) ethane-N,N,N',N'-tetraacetic acid] (Indo-1, 100 microM) and as main anion either chloride or the low-affinity Ca2+ buffer citrate. Intracellular Ca2+ transients (Cai transients) were elicited by depolarizations from a holding potential of -50 mV. In chloride-dialysed cells, Cai transients showed a bell-shaped dependence on the amplitude of the depolarizing pulse. In citrate-dialysed cells, membrane depolarizations were associated with a small rise in [Ca2+]i. These small changes in [Ca2+]i were either followed by a large Cai transient or failed to induce large changes in [Ca2+]i. The peak amplitude of the large Cai transient did not vary with the amplitude of the depolarizing pulse. These results demonstrate that in the presence of intracellular chloride, Ca2+ release in atrial cells is a graded process triggered by Ca2+ influx. Using citrate as the main intracellular anoin, Ca2+ release triggered by Ca2+ entry was no longer graded but occurred in a regenerative manner. The results are discussed in terms of two models in which citrate, affects the spatial distribution of [Ca2+]i or the loading state of the sarcoplasmic reticulum.
authors.affiliation: Laboratory of Physiology, University of Leuven, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Callewaert
authors.forename: K R
authors.initials: KR
authors.lastname: Sipido
authors.forename: E
authors.initials: E
authors.lastname: Carmeliet
authors.forename: L
authors.initials: L
authors.lastname: Pott
authors.forename: P
authors.initials: P
authors.lastname: Lipp
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D003956:Dialysis; D004553:Electric Conductivity; D006168:Guinea Pigs; D006325:Heart Atria / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
chemical_list: D002712:Chlorides; D002951:Citrates; D019343:Citric Acid; D012964:Sodium; D002118:Calcium