36 research outputs found
A new approach to detect and study ion channel formation in microBLMs
No full textIn this paper, an innovative and versatile approach to detect pore formation in microBLMs and to investigate their ion selectivity is described. For the first time, both electrochemical impedance spectroscopy and conductivity measurements are performed on the same membrane, providing a simple, long-lasting and cheap method which can find applications in various ion channel-involving research fields. We make use of this improved experimental procedure to obtain for the first time a range of values to characterize homogeneous polycarbonate-supported microBLMs. To test the validity of our method, the well-known. channel-forming peptide gramicidin D was first employed. Then, we applied our approach to the study of the still unclear membrane interaction mechanisms of the peptides trichogin GA IV and phospholamban, finding that both can form ion channels in biomimetic models. The phospholamban-generated ion channels could be a promising therapeutic target in heart failures and other cardiac diseases. Our methodology might also be useful for detecting new drugs with ion-channel blocking action. (C) 2011 Elsevier B.V. All rights reserved
Ivabradine, coronary artery disease, and heart failure: beyond rhythm control
No full textPietro Scicchitano,1 Francesca Cortese,1 Gabriella Ricci,1 Santa Carbonara,1 Michele Moncelli,1 Massimo Iacoviello,1 Annagrazia Cecere,1 Michele Gesualdo,1 Annapaola Zito,1 Pasquale Caldarola,2 Domenico Scrutinio,3 Rocco Lagioia,3 Graziano Riccioni,4 Marco Matteo Ciccone1 1Section of Cardiovascular Diseases, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Policlinico, Bari, Italy; 2Section of Cardiovascular Diseases, Policlinic, San Paolo Hospital, Bari, Italy; 3Section of Cardiovascular Diseases, Fondazione Maugeri, Cassano Murge, Italy; 4Intensive Cardiology Care Unit, San Camillo de Lellis Hospital, Manfredonia, Foggia, Italy Abstract: Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies. Keywords: chronic heart failure, heart rate reduction, cardiac ischemic disease, heart-rate lowering drugs, funny curren
A Peptide-tethered Lipid Bilayer on Mercury as a Biomimetic System
No full textA novel spacer consisting of a hexapeptide molecule with a high tendency to form a 310-helical structure, which terminates with a sulfydryl group for anchoring to a metal, was tailored for use as a tethered hydrophilic spacer to be interposed between a metal support and a lipid bilayer. The thiol peptide has two triethylenoxy side chains that impart it a satisfactory hydrophilicity and are intended to keep the anchored thiol peptide chains sufficiently apart so as to accommodate water molecules and inorganic ions and to create a suitable environment for the incorporation of integral proteins. This thiol peptide was anchored to a hanging mercury drop electrode. The formation of a phospholipid bilayer on top of the self-assembled thiol peptide was carried out by a novel procedure which exploits the spontaneous tendency of a lipid film to form a bilayer when interposed between two hydrophilic phases. The resulting mercury-supported thiol peptide/lipid bilayer system was characterized by ac voltammetry with phase resolution, chronocoulometry, and impedance spectroscopy. The suitability of this tethered film as a biomembrane model was tested by incorporating ubiquinone-10 and valinomycin
Electrochemical and photoelectrochemical behavior of chlorophyll a films adsorbed on mercury
No full textA Novel Cardiac Bio-Marker: ST2: A Review
No full textCardiovascular diseases (CVD) are the major cause of death worldwide. The identification of markers able to detect the early stages of such diseases and/or their progression is fundamental in order to adopt the best actions in order to reduce the worsening of clinical condition. Brain natriuretic peptide (BNP) and NT-proBNP are the best known markers of heart failure (HF), while troponins ameliorated the diagnosis of acute and chronic coronary artery diseases. Nevertheless, many limitations reduce their accuracy. Physicians have tried to develop further detectable molecules in order to improve the detection of the early moments of CVD and prevent their development. Soluble ST2 (suppression of tumorigenicity 2) is a blood protein confirmed to act as a decoy receptor for interleukin-33. It seems to be markedly induced in mechanically overloaded cardiac myocytes. Thus, HF onset or worsening of a previous chronic HF status, myocardial infarct able to induce scars that make the myocardium unable to stretch well, etc, are all conditions that could be detected by measuring blood levels of soluble ST2. The aim of this review is to explore the possible role of ST2 derived-protein as an early marker of cardiovascular diseases, above all in heart failure and ischemic heart diseases
Superparamagnetic iron oxide nanoparticles (SPIONs) modulate hERG ion channel activity
No full textSuperparamagnetic iron oxide nanoparticles (SPIONs) are widely used in various biomedical applications, such as diagnostic agents in magnetic resonance imaging (MRI), for drug delivery vehicles and in hyperthermia treatment of tumors. Although the potential benefits of SPIONs are considerable, there is a distinct need to identify any potential cellular damage associated with their use. Since human ether à go-go-related gene (hERG) channel, a protein involved in the repolarization phase of cardiac action potential, is considered one of the main targets in the drug discovery process, we decided to evaluate the effects of SPIONs on hERG channel activity and to determine whether the oxidation state, the dimensions and the coating of nanoparticles (NPs) can influence the interaction with hERG channel. Using patch clamp recordings, we found that SPIONs inhibit hERG current and this effect depends on the coating of NPs. In particular, SPIONs with covalent coating aminopropylphosphonic acid (APPA) have a milder effect on hERG activity. We observed that the time-course of hERG channel modulation by SPIONs is biphasic, with a transient increase (∼20% of the amplitude) occurring within the first 1–3 min of perfusion of NPs, followed by a slower inhibition. Moreover, in the presence of SPIONs, deactivation kinetics accelerated and the activation and inactivation I–V curves were right-shifted, similarly to the effect described for the binding of other divalent metal ions (e.g. Cd2+ and Zn2+). Finally, our data show that a bigger size and the complete oxidation of SPIONs can significantly decrease hERG channel inhibition. Taken together, these results support the view that Fe2+ ions released from magnetite NPs may represent a cardiac risk factor, since they alter hERG gating and these alterations could compromise the cardiac action potential
Structure-function relation of phospholamban: modulation of channel activity as a potential regulator of SERCA activity.
No full textPhospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum. When reconstituted in planar lipid bilayers PLN exhibits ion channel activity with a low unitary conductance. From the effect of non-electrolyte polymers on this unitary conductance we estimate a narrow pore with a diameter of ca. 2.2 Å for this channel. This value is similar to that reported for the central pore in the structure of the PLN pentamer. Hence the PLN pentamer, which is in equilibrium with the monomer, is the most likely channel forming structure. Reconstituted PLN mutants, which either stabilize (K27A and R9C) or destabilize (I47A) the PLN pentamer and also phosphorylated PLN still generate the same unitary conductance of the wt/non-phosphorylated PLN. However the open probability of the phosphorylated PLN and of the R9C mutant is significantly lower than that of the respective wt/non-phosphorylated control. In the context of data on PLN/SERCA interaction and on Ca(2+) accumulation in the sarcoplasmic reticulum the present results are consistent with the view that PLN channel activity could participate in the balancing of charge during Ca(2+) uptake. A reduced total conductance of the K(+) transporting PLN by phosphorylation or by the R9C mutation may stimulate Ca(2+) uptake in the same way as an inhibition of K(+) channels in the SR membrane. The R9C-PLN mutation, a putative cause of dilated cardiomyopathy, might hence affect SERCA activity also via its inherent low open probability
