Synergistic actions of glucagon and miniglucagon on Ca2+ mobilization in cardiac cells.
It has been recently shown that the physiological processing of glucagon into its C-terminal (19-29) fragment, miniglucagon, by cardiac cells was essential for the contractile positive inotropic effect of the hormone. However, the mechanisms underlying the effects of miniglucagon remained undetermined. In the present study, we assessed the effects of miniglucagon on Ca2+ homeostasis in embryonic chick ventricular myocytes. In quiescent cells, short-term applications of 0.1 nmol/L miniglucagon markedly increased the accumulation of 45Ca into intracellular compartments resistant to digitonin lysis and sensitive to caffeine. Ca2+ accumulation into the sarcoplasmic reticular (SR) store was further attested by fura 2 imaging studies on quiescent or prestimulated cells: miniglucagon potentiated Ca2+ release from the SR compartment triggered by caffeine and evoked a rise in cytosolic Ca2+ when applied on cells pretreated with 1 mumol/L thapsigargin, a specific inhibitor of the SR Ca2+ pump. Glucagon alone produced a small cytosolic Ca2+ signal that was considerably amplified by miniglucagon. The action of glucagon was mimicked by 8-bromo-cAMP and was blocked by isradipine, suggesting that it relied on the activation of L-type Ca2+ channels, via phosphorylation. We conclude that the combined actions of miniglucagon and glucagon on Ca2+ accumulation into SR stores and Ca2+ release from the same stores are likely to support the positive inotropic effect elicited in vivo by glucagon on heart contraction.
Sauvadet
A
A
INSERM Unité 99, Hôpital Henri Mondor, Créteil, France.
Rohn
T
T
Pecker
F
F
Pavoine
C
C
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D004357:Drug Synergism; D005934:Glucagon / Q000494:pharmacology*; D006352:Heart Ventricles / Q000378:metabolism* / Q000648:ultrastructure; D017275:Isradipine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010446:Peptide Fragments; D015124:8-Bromo Cyclic Adenosine Monophosphate; C039265:glucagon (19-29); D005934:Glucagon; D002118:Calcium; D017275:Isradipine