Cardiovascular depression occurs during the progression of sepsis leading to tissue hypoperfusion, evident in severe cases. Cellular Ca²⁺ dysregulation, which would contribute to decreased cardiac output, has been reported in whole animal models of sepsis (Zhu et al., 2005) and in cellular models where ventricular myocytes are exposed to pro-inflammatory cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β; Duncan et al. 2007). In this study, we investigated changes in gene expression induced in ventricular tissue in a whole animal model of sepsis to assess whether targets involved in excitation-contraction coupling were altered. To model sepsis, male Wistar rats were continuously infused with lipopolysaccharide (LPS, 150 μg/kg/hr) for 24 hr (Gardiner et al. 1995) after which they were anesthetised with halothane and killed humanely by cervical dislocation. The heart was then removed and snap frozen. Cross sections of the whole heart weighing ~ 10 mg were dissected and used for RNA extraction. RT-PCR was performed using TaqMan low-density arrays, data normalised to 18S expression and statistical comparisons made between control and septic transcript levels (t-test). Forty-three transcripts from control (n = 6) and septic (n = 7) hearts were analysed; twenty of the transcripts investigated showed no significant difference between control and septic conditions. These included GAPDH, L-type Ca²⁺ channel, Na⁺ channel Nav 1.5 and caveolin. Ten of the 43 transcripts had significantly higher mean mRNA expression (P< 0.05 control vs septic); expression of inflammatory markers such as TNF-α (P = 0.005) and its type 1 receptor (P = 0.001) were elevated significantly in sepsis, as was IL-1β (P = 0.001) and the nuclear factor kappa light chain gene enhancer (P = 0.022). Thirteen of the 43 targets had significantly lower mean mRNA expression in tissue from septic animals. These included a variety of targets involved in Ca²⁺ regulation; for example SERCA2 (P = 0.008), calsequestrin (P = 0.017), Na⁺/Ca²⁺ exchange (P = 0.004) and the Na⁺/K⁺-ATPase alpha 2 subunit (P = 0.01) were all reduced significantly. Interestingly we also observed that a variety of voltage gated K⁺ channel genes were down regulated including Kv4.2 (P = 0.035), Kv4.3 (P = 0.002), HERG (P = 0.002), and Kir2.1 (P = 0.018). In summary, changes in gene expression occur during the development of sepsis and include targets that are pivotal in regulating cytosolic Ca²⁺ as well as electrical behaviour. If these changes lead to modified protein expression this would contribute to altered excitation-contraction coupling during sepsis.