Ablation of sarcolipin decreases the energy requirements for Ca²⁺ transport by sarco(endo)plasmic reticulum Ca²⁺‐ATPases in resting skeletal muscle

Abstract

a b s t r a c tThe purpose of this study was to examine the effects of sarcolipin (SLN) on sarco(endo) plasmic reticulum Ca 2+ -ATPase (SERCA pump) energetics in vivo and resting skeletal muscle metabolic rate. Using SLN knockout (Sln À/À ) mice we show that SLN ablation increases the transport stoichiometry of SERCA pumps (Ca 2+ uptake/Ca 2+ -ATPase activity) and decreases the relative contribution of SERCA pumps to resting oxygen consumption (VO 2 ) in soleus without affecting soleus or whole body VO 2 . These data suggest that the lower energy requirements for Ca 2+ cycling in resting skeletal muscle of Sln À/À mice do not impact significantly either skeletal muscle or whole body metabolic rate.

The regulation of sarco(endo)plasmic reticulum calcium-ATPases (SERCA)

“…These data suggest that SLN provides additional regulatory control over Ca 2+ handling properties in human cardiac muscle, particularly in regions such as the atria where PLN is absent and under conditions of elevated Ca 2+ concentration (Sahoo et al 2013). Recent evidence also suggests that SLN, but not PLN, may play a role in thermal regulation by promoting uncoupling of the SERCA pump; however, this evidence will be reviewed in the section outlining the regulatory mechanisms of SERCA1a (Bal et al 2012;Sahoo et al 2013;Bombardier et al 2013;Gamu et al 2014).…”

“…Specifically, SLN affects the maximal SERCA-mediated Ca 2+ uptake (V max ) even at high Ca 2+ concentrations, and interacts with SERCA1a throughout the kinetic cycle (Sahoo et al 2013). While SLN was originally considered to be a PLN analogue that regulated SERCA1a in skeletal muscle, recent studies have demonstrated a potential role of SLN in regulating skeletal muscle thermogenesis and whole-body energy metabolism by promoting uncoupling of Ca 2+ transport and ATP hydrolysis (Bal et al 2012;Bombardier et al 2013;Gamu et al 2014). It is suggested that SLN and Ca 2+ bind to SERCA simultaneously, promoting uncoupling of the pump and increasing total energy expenditure (Bal et al 2012;Gamu et al 2014).…”

Persistence of diet-induced obesity despite access to voluntary activity in mice lacking sarcolipin

“…This proportion can be further modified by the SERCA regulatory protein sarcolipin (SLN) (Bombardier et al. 2013b). …”

“…2006) and a recent physiological study (Bombardier et al. 2013b) have shown that SLN can uncouple Ca 2+ transport from ATP hydrolysis, increasing the energy demand by SERCA to pump Ca 2+ . SLN can promote SERCA inefficiency across a range of metabolic rates (Gamu et al.…”

Identification of Small Ankyrin 1 as a Novel Sarco(endo)plasmic Reticulum Ca2+-ATPase 1 (SERCA1) Regulatory Protein in Skeletal Muscle

“…Student's t tests were used to compare sAnk1 (WT) and sAnk1 mutant, sAnk1 (all-L), for co-IP and AFRET experiments with p Ͻ 0.05 being considered significant. Results of assays of ATPase activity were fit to the equation for an allos- (76,77), from data acquired in four experiments conducted on microsomes from three independent transfections. K Ca2ϩ ([Ca 2ϩ ] free resulting in half-maximal activation) was calculated using nonlinear regression analysis.…”