Background: Regulation of L-type Ca 2ϩ channels has important roles in determining the electrical properties of cardiomyocytes. Results: U-II potentiates I Ca,L via U-IIR that couples to the PI3K-dependent PKC␤ 1 isoform. Conclusion: U-IIR stimulation of I Ca,L contributes to the increase in the amplitude of sarcomere shortening. Significance: Regulation of I Ca,L by U-IIR plays important roles in cardiovascular actions including cardiac positive inotropic effects and increasing cardiac output.

Background/Aims: Nesfatin-1 (NF-1), an anorexic nucleobindin-2 (NUCB2)-derived hypothalamic peptide, acts as a peripheral cardiac modulator and it can induce negative inotropic effects. However, the mechanisms underlying these effects in cardiomyocytes remain unclear. Methods: Using patch clamp, protein kinase assays, and western blot analysis, we studied the effect of NF-1 on L-type Ca²⁺ currents (I_Ca,L) and to explore the regulatory mechanisms of this effect in adult ventricular myocytes. Results: NF-1 reversibly decreased I_Ca,L in a dose-dependent manner. This effect was mediated by melanocortin 4 receptor (MC4-R) and was associated with a hyperpolarizing shift in the voltage-dependence of inactivation. Dialysis of cells with GDP-β-S or anti-G_β antibody as well as pertussis toxin pretreatment abolished the inhibitory effects of NF-1 on I_Ca,L. Protein kinase C (PKC) antagonists abolished NF-1-induced responses, whereas inhibition of PKA activity or intracellular application of the fast Ca²⁺-chelator BAPTA elicited no such effects. Application of NF-1 increased membrane abundance of PKC theta isoform (PKC_θ), and PKC_θ inhibition abolished the decrease in I_Ca,L induced by NF-1. Conclusion: These data suggest that NF-1 suppresses L-type Ca²⁺ channels via the MC4-R that couples sequentially to the βγ subunits of G_i/o-protein and the novel PKC_θ isoform in adult ventricular myocytes.

The regimens of LCT administration may have diverse effects on human immune function in different patient populations. However, LCT emulsion at an appropriate dose and infusion speed does not alter human immune function of adult patients undergoing moderate gastrointestinal surgery.