Food restriction promotes downregulation of myocardial L-type Ca²⁺ channels

Abstract

Food restriction (FR) has been shown to impair myocardial performance. However, the mechanisms behind these changes in myocardial function due to FR remain unknown. Since myocardial L-type Ca2+ channels may contribute to the cardiac dysfunction, we examined the influence of FR on L-type Ca2+ channels. Male 60-day-old Wistar rats were fed a control or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was evaluated in isolated left ventricular papillary muscles. The function of myocardial L-type Ca2+ channels was determined by using a pharmacological Ca2+ channel blocker, and changes in the number of channels were evaluated by mRNA and protein expression. FR decreased final body weights, as well as weights of the left and right ventricles. The Ca2+ channel blocker diltiazem promoted a higher blockade on developed tension in FR groups than in controls. The protein content of L-type Ca2+ channels was significantly diminished in FR rats, whereas the mRNA expression was similar between groups. These results suggest that the myocardial dysfunction observed in previous studies with FR animals could be caused by downregulation of L-type Ca2+ channels.

Exercício e restrição alimentar aumentam o RNAm de proteínas do trânsito de Ca2+ miocárdico em ratos

“…Recent data obtained in our laboratory found a significant reduction of protein expression of L-type channel in rats with severe FR, which is contrary to our findings of increased mRNA in the same protein 14 . Therefore, the continuity of these findings will be the determination of the protein expression by Western blot.…”

“…Molecular structures found in the sarcolemma, slow L-type calcium channel (L-channel) and sodium/potassium exchanger (NCX), also found in the sarcoplasmic reticulum, ryanodine channel, the calsequestrin (CQS), the sarcoplasmic reticulum calcium pump (SERCA2a) and phospholamban, are involved in the intracellular calcium handling and participate in the cardiac muscle contraction and relaxation 11 . Studies show that FR decreases the gene expression of ryanodine 12 , SERCA2 13 , L-channel 14 , while physical training (PT) increases the mRNA of SERCA2 [15][16][17] , ryanodine 18,19 and L-channel 20 . The transcription of the molecular structures involved in the intracellular calcium handling can be modulated by thyroid hormones (TH), via nuclear receptors of HT [21][22][23] .…”

Protein Restriction after Weaning Modifies the Calcium Kinetics and Induces Cardiomyocyte Contractile Dysfunction in Rats

“…Thus, this analysis indicates that PR prevents functional adaptations of these regulatory proteins to compensate for deficits in intracellular calcium kinetics, which is an event that is essential for optimal cell mechanical behavior. Indeed, food restriction has been shown to diminish the protein content of L-type Ca 2+ channels [De Tomasi et al, 2009] and the expression and activity of RyR2 receptors in the LV of rats, adaptations involved in intracellular Ca 2+ kinetics dysfunction and, consequently, reduced force and velocity of cell contraction [O'Brien et al, 1995;Vizotto et al, 2007].…”

Influência do tempo de exposição à obesidade sobre a expressão gênica e protéica do sistema regulador do trânsito de cálcio miocárdico

“…(94) O método compreende as seguintes etapas: extração de proteínas, eletroforese em gel, transferência das proteínas do gel para uma membrana de nitrocelulose, identificação das proteínas por anticorpos específicos e quantificação dos blots de polipetídeos. (95) Neste trabalho foi realizada a expressão das proteínas relacionadas com os com o trânsito de cálcio intracelular, ATPase de Ca +2 do retículo sarcoplasmático (SERCA), Fosfolambam (PLB), PLB fosforilado Ser16 (pPLB Ser16), PLB fosforilado Thr17 (pPLB Thr17), CANAL L e Calsequestrina (CSQ). Além disso, foi analisada a expressão da proteína de normalização, β-actina.…”