Figure 2

Impact of GDX on intracellular Ca²⁺-handling mechanisms in ventricular myocytes isolated from rodent hearts. APD is prolonged by GDX, due to a decrease in repolarizing K⁺ currents (I_Kur) and a reduction in the expression of Kv1.5. Reduced Ca²⁺ influx along with smaller Ca²⁺ sparks attenuates SR Ca²⁺ release. Ca²⁺ transient decay is slowed by longer APs and slower SR Ca²⁺ uptake mediated by a decrease in phosphorylation of PLB by CaMKII (and possibly PKA). Peak contractions are attenuated through smaller peak Ca²⁺ transients and a decrease in maximal myofilament responsiveness to Ca²⁺. Contractions are slowed because SR Ca²⁺ uptake is reduced and the slower β-MHC isoform predominates. Whether NCX activity or expression is affected by GDX is not yet clear.