부산대학교 도서관

Previous studies demonstrated higher systolic intracellular [Ca.sup.2+] concentration ([[Ca.sup.2+]]i) amplitudes result in faster [[Ca.sup.2+]].sub.i] decline rates, as does [beta]-adrenergic ([beta]-AR) stimulation. The purpose of this study is to determine the major factor responsible for the faster [[Ca.sup.2+]].sub.i] decline rate with [beta]-AR stimulation, the increased systolic [Ca.sup.2+] concentration levels, or phosphorylation of phospholamban. Mouse myocytes were perfused under basal conditions [ 1 mM extracellular [Ca.sup.2+] concentration ([[Ca.sup.2+]]o)], followed by high extracellular [Ca.sup.2+] (3 mM [[Ca.sup.2+]]o), washout with 1 mM [[Ca.sup.2+]]o, followed by 1 [micro]M isoproterenol (ISO) with 1 mM [[Ca.sup.2+]].sub.o]. ISO increased [Ser.sup.16] phosphorylation compared with 3 mM [[Ca.sup.2+]].sub.o], whereas [Thr.sup.17] phosphorylation was similar. [Ca.sup.2+] transient (CAT) (fluo 4) data were obtained from matched CaT amplitudes with 3 mM [[Ca.sup.2+]].sub.o] and ISO. [[Ca.sup.2+]].sub.i] decline was significantly faster with ISO compared with 3 mM [[Ca.sup.2+]].sub.o]. Interestingly, the faster decline with ISO was only seen during the first 50% of the decline. CaT time to peak was significantly faster with ISO compared with 3 mM [[Ca.sup.2+]].sub.o]. A [Ca.sup.2+]/calmodulin-dependent protein kinase (CAMKII) inhibitor (KN-93) did not affect the CaT decline rates with 3 mM [[Ca.sup.2+]].sub.o] or ISO but normalized ISO's time to peak with 3 mM [[Ca.sup.2+]].sub.o]. Thus, during [beta]-AR stimulation, the major factor for the faster CaT decline is due to [Ser.sup.16] phosphorylation, and faster time to peak is due to CAMKII activation. phospholamban; phosphorylation; ryanodine receptor; sarcoplasmic reticulum calcium ion-adenosinetriphosphatase; calcium ion/calmodulin-dependent protein kinase doi: 10.1152/ajpheart.00402.2011.