1,25 Dihydroxyvitamin D3 affects calmodulin distribution among subcellular fractions of skeletal muscle

Abstract

1,25 Dihydroxyvitamin D3 has been shown to stimulate calcium fluxes across skeletal muscle membranes. The involvement of calmodulin in the effects of the metabolite was investigated. Primary cultures of chick embryo skeletal muscle myoblasts and soleus muscles from vitamin D-deficient or 1,25 (OH)2D3-treated chicks were used. Culture of myoblasts and vitamin D-deficient soleus with 1,25 (OH)2D3 (0.05 ng/ml) for 24 and 1 hour, respectively, significantly increased 45Ca uptake by the preparations. In the presence of the calmodulin antagonists flufenazine or compound 48/80 in the uptake medium, no differences between control and treated cultures were observed. The calmodulin content of myoblasts and soleus homogenates and subcellular fractions derived therefrom was estimated by measuring their capacity to stimulate calmodulin-depleted cAMP phosphodiesterase. No changes in total calmodulin cellular content could be detected in response to 1,25(OH)2D3. However, the sterol produced an increase in calmodulin levels of microsomes, mitochondria, and crude myofibrillar fraction and a proportional decrease in cytosolic calmodulin concentration. The 1,25(OH)2D3-dependent changes in calmodulin distribution among subcellular fractions of soleus muscle were observed either in vivo or in vitro. The effects in vitro were already detectable after 5 minutes of treatment with the sterol and parallel 1,25(OH)2D3-dependent changes in tissue Ca uptake. The results suggest that changes in calmodulin intracellular distribution may underly part of the mechanism by which 1,25(OH)2D3 affects muscle calcium transport.

Calmodulin in Neurotransmitter and Hormone Action

“…In parallel with the increase in 45Ca uptake, there was an increase of CaM in the microsomal, mitochondrial and myofibrillar fractions and a concomitant decrease in the cytosol (87). In parallel with the increase in 45Ca uptake, there was an increase of CaM in the microsomal, mitochondrial and myofibrillar fractions and a concomitant decrease in the cytosol (87).…”

“…In skeletal muscle, as in intestine, calcitriol increases Ca 2+ fluxes through a nongenomic as well as a genomic mechanism (87). In chick embryo skeletal muscle myoblasts and vitamin D-deficient soleus muscle, calcitriol-increased 45…”

Vitamin D supplementation does not improve human skeletal muscle contractile properties in insufficient young males

“…Emerging data now suggest at a cellular level that skeletal muscle is indeed a tissue that responds functionally to vitamin D. recent data have demonstrated in vivo improvements in mitochondrial oxidative function when severe vitamin D deficiency is corrected in humans (Sinha et al 2013). Moreover, studies in chick embryo myoblast cultures have provided robust evidence that vitamin D is a regulator of intracellular ca 2+ concentration (capiati et al 2000;Morelli et al 1993), which has also been observed in vivo in chicks (Vazquez et al 1995) and in vitro in fully differentiated soleus muscle (de Boland et al 1988). Vitamin D may therefore be implicated in skeletal muscle contractility, which early reports from vitamin D depleted rats have alluded to (rodman and Baker 1978).…”

Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction?

“…Possible linkages to vitamin D in the brain have not been specifically examined for calmodulin, another important calcium-binding protein in the brain (129), although two studies reported that calcitriol treatment shifted the intracellular distribution of calmodulin (130) and that calmodulin is involved in calcitriolregulated intracellular calcium homeostasis (131) in chick embryo muscle cells. In the brain, calmodulin is involved in neurotransmitter activity (132), NMDAinduced synaptic plasticity (133), and short-term plasticity (transient alteration of the efficiency of synaptic transmission between neurons) (134).…”