Alterations in phospholipid metabolism in blood elements have been proposed as the possible biochemical marker of schizophrenia. In the present study, we investigated the composition and membrane distribution of phospholipids in platelets of drug-free schizophrenic patients and controls. We have demonstrated that platelets of drug-free schizophrenics have significantly higher cytosolic Ca2+ levels in comparison with healthy controls. Platelets of drug-free schizophrenic patients have a lower content of phosphatidylinositol (PI). After thrombin activation, PI is the target of phospholipase C instead of phosphatidylinositol 4,5-bisphosphate (PIP2), which is hydrolyzed in platelets of controls. Alterations in the distribution of phospholipids were found in the plasma membrane of platelets of schizophrenic patients. We suggest that alterations in phospholipid metabolism might be evoked by a disturbance of calcium homeostasis in schizophrenic patients.
Hydrogen peroxide injected into the inflow cannula of isolated ventilated rat lungs produced a dose-dependent vasoconstriction in the range 0.25-10 mM, with maximum response between 2 - 5 mM. The effects of H2O2 can be influenced by ionophores or specific inhibitors of ionic channels or pumps. A key role is played by sodium ions which govern the subsequent inflow or outflow of calcium, an ion mediating the vasoconstriction. A physiological role for H2O2 generated by NADPH oxidase is postulated.
We present a review about the relationship between ryanodine receptors and voltage-gated calcium channels in myocardium, and also how both of them are related to protein kinase A. Ryanodine receptors, which have three subtypes (RyR1-3), are located on the membrane of sarcoplasmic reticulum. Different subtypes of voltage-gated calcium channels interact with ryanodine receptors in skeletal and cardiac muscle tissue. The mechanism of excitation-contraction coupling is therefore different in the skeletal and cardiac muscle. However, in both tissues ryanodine receptors and voltage-gated calcium channels seem to be physically connected. FK-506 binding proteins (FKBPs) are bound to ryanodine receptors, thus allowing their concerted activity, called coupled gating. The activity of both ryanodine receptors and voltage-gated calcium channels is positively regulated by protein kinase A. These effects are, therefore, components of the mechanism of sympathetic stimulation of myocytes. The specificity of this enzyme’s targeting is achieved by using different A kinase adapting proteins. Different diseases are related to inborn or acquired changes in ryanodine receptor activity in cardiac myocytes. Mutations in the cardiac ryanodine receptor gene can cause catecholamine-provoked ventricular tachycardia. Changes in phosphorylation state of ryanodine receptors can provide a credible explanation for the development of heart failure. The restoration of their normal level of phosphorylation could explain the positive effect of beta-blockers in the treatment of this disease. In conclusion, molecular interactions of ryanodine receptors and voltage-gated calcium channels with PKA have a significant physiological role. However, their defects and alterations can result in serious disturbances., M. M. Petrovič, K. Valeš, B. Putnikovič, V. Djulejič, D. M. Mitrovič., and Obsahuje bibliografii a bibliografické odkazy
Plasma endothelin-1 (ET-1) levels are elevated in spinal cord injury (SCI), and ET-1 may be involved in the pathophysiology of this condition. However, its effects on contractile function of the heart of SCI rats are still unknown. To define more clearly the possiblel role of ET-1 following SCI, we investigated the effect of ET-1 on the contraction, calcium transients and L-type calcium current (ICa,L) in the cardiomyocytes of control and SCI rats. Sixteen Sprague-Dawley male rats aged 80-100 days and weighing 250-350 g were randomized into control and SCI groups. Fourteen days following compression injury to the spinal cord, effects of ET-1 on the contraction, calcium transients and ICa,L were studied in the cardiomyocytes of control and SCI rats by the technique of simultaneous measurement of intracellular Ca2+ and contraction and by whole-cell configuration of the patch-clamp technique. In myocytes from control rats, ET-1 significantly increased contraction, the magnitude of Ca2+ transients and the peak amplitude of ICa,L. However, ET-1 had little effect on the amplitude of contraction, calcium transients and ICa,L in myocytes from SCI rats. These results suggest that the positive inotropic effects of ET-1 on control myocardial contraction may be altered in pathological states such as SCI., Y.-F. Guo ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Chronic kidney disease (CKD) is associated with increased concentration of intracellular calcium, which is pathological and may lead to irreversible damage of cell functions and structures. The aim of our study was to investigate the impact of 6 months vitamin D3 supplementation (14 000 IU/week) on free cytosolic calcium concentration ([Ca2+]i) and on the plasma membrane calcium ATPase (PMCA) activity of patients with CKD stage 2-3. PMCA activity of patients was also compared to that of healthy volunteers. Vitamin D3 supplementation of CKD patients resulted in the decrease of [Ca2+]i (119.79±5.87 nmol/l vs. 105.36± 3.59 nmol/l, n=14, P<0.001), whereas PMCA activity of CKD patients (38.75±22.89 nmol Pi/mg/h) remained unchanged after vitamin D3 supplementation (40.96±17.74 nmol Pi/mg/h, n=14). PMCA activity of early stage CKD patients before supplementation of vitamin D3, was reduced by 34 % (42.01±20.64 nmol Pi/mg/h) in comparison to healthy volunteers (63.68±20.32 nmol Pi/mg/h, n=28, P<0.001). These results indicate that vitamin D3 supplementation had a lowering effect on [Ca2+]i and negligible effect on PMCA activity in CKD patients., M. Morvová Jr., I. Lajdová, V. Spustová, M. Zvarík, L. Šikurová., and Obsahuje bibliografii
ncreased systemic vascular resistance is responsible for blood pressure (BP) elevation in most forms of human or experimental hypertension. The enhanced contractility of structurally remodeled resistance arterioles is mediated by enhanced calcium entry (through L type voltagedependent calcium channels - L-VDCC) and/or augmented calcium sensitization (mediated by RhoA/Rho kinase pathway). It is rather difficult to evaluate separately the role of these two pathways in BP control because BP response to the blockade of either pathway is always dependent on the concomitant activity of the complementary pathway. Moreover, vasoconstrictor systems enhance the activity of both pathways, while vasodilators attenuate them. The basal fasudil-sensitive calcium sensitization determined in rats deprived of endogenous renin-angiotensi n system (RAS) and sympathetic nervous system (SNS) in wh ich calcium entry was dose- dependently increased by L-VDCC opener BAY K8644, is smaller in spontaneously hypertensive rats (SHR) than in normotensive Wistar-Kyoto (WKY) rats. In co ntrast, if endogenous RAS and SNS were present in intact rats, fasudil caused a greater BP fall in SHR than WKY rats. Our in vivo experiments indicated that the endogenous pressor systems (RAS and SNS) augment calcium sensitization mediated by RhoA/Rho kinase pathway, whereas the endogenous vasodilator systems (such as nitric oxide) attenuate this pathway. However, the modulation of calcium entry and calcium sensitization by nitric oxide is strain-dependent because NO deficiency significan tly augments low calcium entry in WKY and low calcium sensitization in SHR. Further in vivo and in vitro experiments should clarify the interrelationships between endogenous vasoactive systems an d the contribution of calcium entry and/or calcium sensitization to BP maintenance in various forms of experimental hypertension., J. Zicha ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy