Inhibition of the sarcolemmal Ca2+ pump in embryonic chick heart cells by mini-glucagon.
The effect of mini-glucagon, the metabolite (19-29) of glucagon was examined on the sarcolemmal (SL) Ca2+ pump activity measured in situ, in single quiescent embryonic chick heart ventricular cells loaded with Fura-2. The method consisted in triggering limited cytosolic Ca2+ concentration ([Ca2+]i) pulses by the addition of the Ca2+ ionophore 4-bromo-A23187. [Ca2+]i decays, imposed by the addition of EGTA, were monitored in conditions in which only the SL Ca2+ pump could ensure [Ca2+]i removal, i.e. in the presence of the sarcoplasmic reticular (SR) Ca2+ pump specific inhibitor, thapsigargin, substituting NaCI by LiCI in the external medium in order to quench the Na+/Ca2+ exchanger, and under null Ca2+ gradient. Mini-glucagon elicited a dose-dependent inhibition of the SL Ca2+ pump, maximal 80% inhibition being observed with 1 nM mini-glucagon. In addition to its effect on the SL Ca2+ pump, mini-glucagon evoked a delayed onset of a [Ca2+]i oscillatory response in cells incubated in normal conditions. Both effects of mini-glucagon were mimicked by vanadate tested at 2 microM, a concentration at which it acts as a specific inhibitor of the SL Ca2+ pump. These results define the contribution of the cardiac sarcolemmal Ca2+ pump to Ca2+ homeostasis in situ and its role as a target for mini-glucagon action.
Sauvadet
A
A
INSERM Unité 99, Hôpital Henri Mondor, Créteil, France.
Pecker
F
F
Pavoine
C
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D002642:Chick Embryo; D005934:Glucagon / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D012508:Sarcolemma / Q000187:drug effects* / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D010446:Peptide Fragments; D014638:Vanadates; C039265:glucagon (19-29); D005934:Glucagon; D000252:Calcium-Transporting ATPases; D002118:Calcium