O Casis

Universidad del País Vasco / Euskal Herriko Unibertsitatea, Leioa, Basque Country, Spain

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Publications (50)146.15 Total impact

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    ABSTRACT: Cardiac arrhythmias are one of the main causes of death worldwide. Several studies have shown that inflammation plays a key role in different cardiac diseases and Toll-like receptors (TLRs) seem to be involved in cardiac complications. In the present study, we investigated whether the activation of TLR4 induces cardiac electrical remodeling and arrhythmias, and the signaling pathway involved in these effects. Membrane potential was recorded in Wistar rat ventricle. Ca(2+) transients, as well as the L-type Ca(2+) current (ICaL) and the transient outward K(+) current (Ito), were recorded in isolated myocytes after 24h exposure to the TLR4 agonist, lipopolysaccharide (LPS, 1μg/ml). TLR4 stimulation in vitro promoted a cardiac electrical remodeling that leads to action potential prolongation associated with arrhythmic events, such as delayed afterdepolarization and triggered activity. After 24h LPS incubation, Ito amplitude, as well as Kv4.3 and KChIP2 mRNA levels were reduced. The Ito decrease by LPS was prevented by inhibition of interferon regulatory factor 3 (IRF3), but not by inhibition of interleukin-1 receptor-associated kinase 4 (IRAK4) or nuclear factor kappa B (NF-κB). Extrasystolic activity was present in 25% of the cells, but apart from that, Ca(2+) transients and ICaL were not affected by LPS; however, Na(+)/Ca(2+) exchanger (NCX) activity was apparently increased. We conclude that TLR4 activation decreased Ito, which increased AP duration via a MyD88-independent, IRF3-dependent pathway. The longer action potential, associated with enhanced Ca(2+) efflux via NCX, could explain the presence of arrhythmias in the LPS group.
    Journal of Molecular and Cellular Cardiology 08/2014; · 5.15 Impact Factor
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    ABSTRACT: Over the last years zebrafish has become a popular model in the study of cardiac physiology, pathology and pharmacology. Recently, the application of the 3Rs regulation and the characteristics of the embryo have reduced the use of adult zebrafish use in many studies. However, the zebrafish embryo cardiac physiology is poorly characterized since most works have used indirect techniques and direct recordings of cardiac action potential and ionic currents are scarce. In order to optimize the zebrafish embryo model, we used electrophysiological, pharmacological and immunofluorescence tools to identify the characteristics and the ionic channels involved in the ventricular action potentials of zebrafish embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated the cardiac electrical activity, indicating that the action potential upstroke depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type Ca(+2) channels since it is abolished by specific blockade. The direct channel blockade indicates that the action potential repolarization and diastolic potential depends on ERG K(+) channels. The presence in the embryonic heart of the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by immunofluorescence, while the absence of effect of specific blockers and immunostaining indicate that two K(+) repolarizing currents present in human heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results describe the ionic channels present and its role in the zebrafish embryo heart and support the use of zebrafish embryos to study human diseases and their use for drug testing.
    Pharmacological Research 04/2014; · 4.35 Impact Factor
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    ABSTRACT: GRP94 is a member of the heat shock protein family normally confined to the endoplasmic reticulum that sometimes escapes the KDEL-mediated retention system. It is overexpressed in some gastric and other gastrointestinal carcinomas, but little is known about the physiological role of GRP94 in gastric mucosa. We investigated the membrane presence of GRP94 in parietal cells, which secrete acid into the gastric lumen, using subcellular fractionation, selective solubilization of membrane proteins, Western blotting, and radio-ligand binding and provided evidence of functional GRP94 expression at the surface of gastric mucosa parietal cells anchored to the basolateral domain. Our results show that GRP94 is not an integral membrane protein since 50 mM Na2CO3 treatment dissociates part of it from the membrane. However, 100 mM Na2CO3 treatment did not extract all GRP94 from the membrane, which indicates that it is strongly associated with it. The presence of GRP94 in isolated plasma membrane was demonstrated by Western blotting and its functionality by radio-ligand binding experiments. Both the KD value obtained in saturation experiments with N-ethylcarboxamido-[3H]adenosine at 4°C, at the nanomolar range, and the inhibition constant of its binding by radicicol, the most specific GRP94 inhibitor, indicate that active receptor regions are exposed at the membrane surface. Western blotting of plasma membrane subfractions showed that GRP94 is mainly expressed in the basolateral membrane of gastric parietal cells, while its presence in the apical domain is negligible, thereby inferring a role for GRP94 in processes operating in this membrane domain.
    Biochemistry (Moscow) 01/2014; 79(1):8-15. · 1.15 Impact Factor
  • Pharmacological Research. 01/2014;
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    ABSTRACT: The heart must constantly adapt its activity to the needs of the body. In any potentially dangerous or physically demanding situation the activated sympathetic nervous system leads a very fast cardiac response. Under these circumstances, 1-adrenergic receptors activate intracellular signaling pathways that finally phosphorylate the caveolae-located subpopulation of Kv4 channels and reduce the transient outward K(+) current (Ito) amplitude. This reduction changes the shape of the cardiac action potential and makes the plateau phase to start at higher voltages. This means that there are more calcium ions entering the myocyte and the result is an increase in the strength of the contraction. However, an excessive reduction of Ito could dangerously prolong action potential duration and this could cause arrhythmias when the heart rate is high. This excessive current reduction does not occur because there is a second population of Ito channels located in non-caveolar membrane rafts that are not accessible for α1-AR mediated regulation. Thus, the location of the components of a given transduction signaling pathway in membrane domains determines the correct and safe behavior of the heart. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters.
    Biochimica et Biophysica Acta 06/2013; · 4.66 Impact Factor
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    ABSTRACT: Background/Aims: In diabetic ventricular myocytes, transient outward potassium current (I(to)) amplitude is severely reduced because of the impaired catecholamine release that characterizes diabetic autonomic neuropathy. Sympathetic nervous system exhibits a trophic effect on I(to) since incubation of myocytes with noradrenaline restores current amplitude via beta-adrenoceptor (βAR) stimulation. Here, we investigate the intracellular signalling pathway though which incubation of diabetic cardiomyocytes with the βAR agonist isoproterenol recovers I(to) amplitude to normal values. Methods: Experiments were performed in ventricular myocytes isolated from streptozotocin-diabetic rats. I(to) current was recorded by using the patch-clamp technique. Kv4 channel expression was determined by immunofluorescence. Protein-protein interaction was determined by coimmunoprecipitation. Results: Stimulation of βAR activates first a Gαs protein, adenylyl cyclase and Protein Kinase A. PKA-phosphorylated receptor then switches to the Gαi protein. This leads to the activation of the βAR-Kinase-1 and further receptor phosphorylation and arrestin dependent internalization. The internalized receptor-arrestin complex recruits and activates cSrc and the MAPK cascade, where Ras, c-Raf1 and finally ERK1/2 mediate the increase in Kv4.2 and Kv4.3 protein abundance in the plasma membrane. Conclusion: β(2)AR stimulation activates a Gαs and Gαi protein dependent pathway where the ERK1/2 modulates the Ito current amplitude and the density of the Kv4.2 and Kv4.2 channels in the plasma membrane upon sympathetic stimulation in diabetic heart.
    Cellular Physiology and Biochemistry 01/2013; 31(1):25-36. · 3.42 Impact Factor
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    ABSTRACT: AIMS: The fast transient outward current, I(to,fast) , is the most extensively studied cardiac K(+) current in diabetic animals. Two hypotheses have been proposed to explain how type-1 diabetes reduces this current in cardiac muscle. The first one is a deficiency in channel expression due to a defect in the trophic effect of insulin. The second one proposes flawed glucose metabolism as the cause of the reduced I(to,fast) . Moreover, little information exists about the effects and possible mechanisms of diabetes on the other repolarizing currents of the human heart: I(to,slow) , I(K) (r) , I(K) (s) , I(K) (ur) , I(K) (slow) and I(K) (1) . METHODS: We recorded cardiac action potentials and K(+) currents in ventricular cells isolated from control and streptozotocine- or alloxan-induced diabetic mice and rabbits. Channel protein expression was determined by immunofluorescence. RESULTS: Diabetes reduces the amplitude of I(to,fast) , I(to,slow) and I(K) (slow) , in ventricular myocytes from mouse and rabbit, with no effect on I(ss) , I(K) (r) or I(K) (1) . The absence of changes in the biophysical properties of the currents and the immunofluorescence experiments confirmed the reduction in channel protein synthesis. Six hours incubation of myocytes with insulin or piruvate recovered current amplitudes and fluorescent staining. The activation of AMP-K reduced the same K(+) currents in healthy myocytes and prevented the piruvate-induced current recovery. CONCLUSION: Diabetes reduces K(+) current densities in ventricular myocytes due to a defect in channel protein synthesis. Activation of AMP-K secondary to deterioration in the metabolic status of the cells is responsible for K(+) channel reductions. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.
    Acta Physiologica 11/2012; · 4.38 Impact Factor
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    ABSTRACT: Cardiac sodium channel β-subunit mutations have been associated with several inherited cardiac arrhythmia syndromes. To identify and characterize variations in SCN1Bb associated with Brugada syndrome (BrS) and sudden infant death syndrome (SIDS). All known exons and intron borders of the BrS-susceptibility genes were amplified and sequenced in both directions. Wild type (WT) and mutant genes were expressed in TSA201 cells and studied using co-immunoprecipitation and whole-cell patch-clamp techniques. Patient 1 was a 44-year-old man with an ajmaline-induced type 1 ST-segment elevation in V1 and V2 supporting the diagnosis of BrS. Patient 2 was a 62-year-old woman displaying a coved-type BrS electrocardiogram who developed cardiac arrest during fever. Patient 3 was a 4-month-old female SIDS case. A R214Q variant was detected in exon 3A of SCN1Bb (Na(v)1B) in all three probands, but not in any other gene previously associated with BrS or SIDS. R214Q was identified in 4 of 807 ethnically-matched healthy controls (0.50%). Co-expression of SCN5A/WT + SCN1Bb/R214Q resulted in peak sodium channel current (I(Na)) 56.5% smaller compared to SCN5A/WT + SCN1Bb/WT (n = 11-12, P<0.05). Co-expression of KCND3/WT + SCN1Bb/R214Q induced a Kv4.3 current (transient outward potassium current, I(to)) 70.6% greater compared with KCND3/WT + SCN1Bb/WT (n = 10-11, P<0.01). Co-immunoprecipitation indicated structural association between Na(v)β1B and Na(v)1.5 and K(v)4.3. Our results suggest that R214Q variation in SCN1Bb is a functional polymorphism that may serve as a modifier of the substrate responsible for BrS or SIDS phenotypes via a combined loss of function of sodium channel current and gain of function of transient outward potassium current.
    Heart rhythm: the official journal of the Heart Rhythm Society 12/2011; 9(5):760-9. · 4.56 Impact Factor
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    ABSTRACT: To identify the causes for the inhomogeneity of ventricular repolarization and increased QT dispersion in hypothyroid mice. We studied the effects of 5-propyl-2-thiouracil-induced hypothyroidism on the ECG, action potential (AP) and current density of the repolarizing potassium currents I(to,fast), I(to,slow), I(K,slow) and I(ss) in enzymatically isolated myocytes from three different regions of mouse heart: right ventricle (RV), epicardium of the left ventricle (Epi-LV) and interventricular septum. K(+) currents were recorded with the patch-clamp technique. Membranes from isolated ventricular myocytes were extracted by centrifugation. Kv4.2, Kv4.3, KChIP and Na/Ca exchanger proteins were visualized by Western blot. The frequency or conduction velocity was not changed by hypothyroidism, but QTc was prolonged. Neither resting membrane potential nor AP amplitude was modified. The action potential duration (APD)(90) increased in the RV and Epi-LV, but not in the septum. Hypothyroid status has no effect either on I(to,slow), I(k,slow) or I(ss) in any of the regions analysed. However, I(to,fast) was significantly reduced in the Epi-LV and in the RV, whereas it was not altered in cells from the septum. Western blot analysis reveals a reduction in Kv4.2 and Kv4.3 protein levels in both the Epi-LV and the RV and an increase in Na/Ca exchanger. From these results we suggest that the regional differences in APD lengthening, and thus in repolarization inhomogeneity, induced by experimental hypothyroidism are at least partially explained by the uneven decrease in I(to,fast) and the differences in the relative contribution of the depolarization-activated outward currents to the repolarization process.
    Acta Physiologica 09/2011; 204(4):502-12. · 4.38 Impact Factor
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    ABSTRACT: KCNE1 encodes an auxiliary subunit of cardiac potassium channels. Loss-of-function variations in this gene have been associated with the LQT5 form of the long QT syndrome (LQTS), secondary to reduction of I(Ks) current. We present a case in which a D85N rare polymorphism in KCNE1 is associated with an LQT2 phenotype. An 11-year old competitive athlete presented with mild bradycardia and a QTc interval of 470 ms. An LQT2 phenotype, consisting of low-voltage bifid T waves, was evident in the right precordial electrocardiogram leads. During the tachycardia phase following adenosine, QTc increased to 620 ms. Genetic analysis revealed a rare heterozygous polymorphism in KCNE1 predicting the substitution of asparagine for aspartic acid at position 85 of minK (D85N). Patch clamp experiments showed that KCNE1-D85N, when co-expressed with KCNH2 in TSA201 cells, significantly reduced I(Kr). Homozygous co-expression of the mutant with KCNH2 reduced I(Kr) tail current by 85%, whereas heterozygous co-expression reduced the current by 52%, demonstrating for the first time a dominant-negative effect of D85N to reduce I(Kr). Co-expression of the mutant with KCNQ1, either homozygously or heterozygously, produced no change in I(Ks). Our results suggest that a rare polymorphism KCNE1-D85N underlies the development of an LQT2 phenotype in this young athlete by interacting with KCNH2 to cause a dominant-negative effect to reduce I(Kr). Our data provide further evidence in support of the promiscuity of potassium channel β subunits in modulating the function of multiple potassium channels leading to a diversity of clinical phenotypes.
    Europace 06/2011; 13(10):1478-83. · 2.77 Impact Factor
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    ABSTRACT: M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC), a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function.
    PLoS ONE 01/2011; 6(9):e25508. · 3.53 Impact Factor
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    ABSTRACT: In ventricular myocytes, α1-AR stimulates Gαs proteins and reduces the transient outward K(+) current (I(to)) via a cAMP/PKA-mediated pathway and thus regulates cardiac contraction and excitability. This I(to) reduction is compartmentalized and limited to discrete membrane regions since PKA-dependent phosphorylation of the I(to) channels after α1-AR stimulation requires the integrity of both the sarcoplasmic membrane and the cytoskeleton. The aim of this work was to investigate the mechanisms involved in the compartmentalization of the PKA-dependent modulation of I(to) in response to α1-AR activation. I(to) current recordings were performed by the Patch-Clamp technique. Membrane rafts from isolated ventricular myocytes were extracted by centrifugation in a sucrose density gradient. The different proteins were visualized by western blot and protein-protein interactions determined by coimmunoprecipitation experiments. Localization of I(to) channel in caveolae, particular subtypes of membrane rafts, was achieved by electron microscopy. Patch-Clamp recordings show that a functional supramolecular complex, kept together by the Akinase anchoring protein AKAP100, exist in caveolae in living myocytes. Density gradients and immunoprecipitation experiments show that the components of the α1-AR/I(to) pathway localize in caveolae, forming two different groups of proteins. The K(V)4.2/K(V)4.3 channel forms a supramolecular complex with PKA through AKAP100 and is attached to caveolae by interacting with caveolin-3. On the other hand, α1-AR, Gαs and adenylate cyclase gather in a second group also connected to caveolin-3. Therefore, both groups of preassembled proteins are maintained in close proximity by caveolin-3. A different I(to) channel population localizes in non-caveolar membrane rafts and is not sensitive to α1-adrenergic regulation.
    Channels (Austin, Tex.) 05/2010; 4(3):168-78. · 1.91 Impact Factor
  • Biophysical Journal 01/2010; 98(3). · 3.67 Impact Factor
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    ABSTRACT: Diabetic patients have a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death, and show important alterations in the electrocardiogram, most of these related to the repolarization. In myocytes isolated from diabetic hearts, the transient outward K+ current (Ito) is the repolarizing current that is mainly affected. Type 1 diabetes alters Ito at 3 levels: the recovery of inactivation, the responsiveness to physiologic regulators, and the functional expression of the channel. Diabetes slows down Ito recovery of inactivation because it triggers the switching from fast-recovering Kv4.x channels to the slow-recovering Kv1.4. Diabetic animals also have decreased responsiveness of Ito towards the sympathetic nervous system; thus, the diabetic heart develops a resistance to its physiologic regulator. Finally, diabetes impairs support of various trophic factors required for the functional expression of the channel and reduces Ito amplitude by decreasing the amount of Kv4.2 and Kv4.3 proteins.
    Canadian Journal of Physiology and Pharmacology 03/2009; 87(2):77-83. · 1.56 Impact Factor
  • Biophysical Journal 01/2009; 96(3). · 3.67 Impact Factor
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    ABSTRACT: One of the most common symptoms of diabetes is extreme hunger, but the brain mechanism underlying this hyperphagia is unknown. The endocannabinoid system has emerged as one of the main food intake regulators in the brain. However, the effects of type 1 diabetes on the endocannabinoid system are not completely known. Thus, the aim of the present work is to establish the possible alterations induced by type 1 diabetes on the brain endocannabinoid system in rats. Western blot and immunocytochemistry were used to measure CB1 and phosphorylated CB1 receptor expression in several prosencephalic regions in streptozotocin-induced type 1 diabetic rats. Serum leptin levels were measured by ELISA. CB1 receptor expression was increased in striatum and hypothalamus of diabetic animals, with no changes in other brain areas studied. CB1 receptor phosphorylation was also increased in the same brain areas. Type 1 diabetes induced significant weight loss, and serum leptin levels were severely decreased. These results reinforce the possible role of the CB1 receptor as a pharmacological target for the clinical management of appetite in diabetic patients.
    Hormone and Metabolic Research 08/2008; 40(7):454-8. · 2.15 Impact Factor
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    ABSTRACT: In myocytes from diabetic hearts, the reduction in the amplitude of the transient outward potassium current (I(to)) and the acceleration of its inactivation contribute to the action potential duration lengthening. Whereas the reduced amplitude is attributable to a reduced support of trophic factors, the mechanism underlying the acceleration of inactivation remains unknown. Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) modifies the inactivation kinetics of I(to). In this work we explored the role of CaMKII in the acceleration of I(to) current inactivation observed in diabetic myocytes. We used patch-clamp and immunoblotting techniques in enzymatically-isolated myocytes from healthy and streptozotocin-induced diabetic rat hearts, and in blood samples from diabetic patients. In control myocytes, inhibition of either calmodulin or CaMKII accelerated I(to) current inactivation. However, in diabetic myocytes I(to) inactivation was already accelerated, and did not respond to calmodulin or CaMKII inhibition. Calmodulin protein abundance was significantly reduced in diabetic myocytes. Incubation of diabetic myocytes with insulin recovered calmodulin expression to normal values. A similar pattern of calmodulin expression appears in the blood of diabetic patients. Insulin treatment also restored I(to) current inactivation kinetics as well as the responsiveness to regulation by calmodulin. Diabetes-induced acceleration of I(to) current inactivation is due to a reduced effect of CaMKII on I(to) channels as a result of a diabetes-induced reduction in calmodulin protein expression. A correct follow up of the insulin treatment could prevent this alteration.
    Cellular Physiology and Biochemistry 02/2008; 22(5-6):625-34. · 3.42 Impact Factor
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    ABSTRACT: Cardiac ion channelopathies are responsible for an ever-increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST-segment elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death. Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b (Ca(v beta2b)), CACNA2D1 (Ca(v alpha2delta1)), and CACNA1C tagged with enhanced yellow fluorescent protein (Ca(v)1.2). Whole-cell patch-clamp studies were performed after 48 to 72 hours. Three probands displaying ST-segment elevation and corrected QT intervals < or = 360 ms had mutations in genes encoding the cardiac L-type calcium channel. Corrected QT ranged from 330 to 370 ms among probands and clinically affected family members. Rate adaptation of QT interval was reduced. Quinidine normalized the QT interval and prevented stimulation-induced ventricular tachycardia. Genetic and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the alpha1- and beta2b-subunits of the L-type calcium channel. Confocal microscopy revealed a defect in trafficking of A39V Ca(v)1.2 channels but normal trafficking of channels containing G490R Ca(v)1.2 or S481L Ca(v beta2b)-subunits. This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals.
    Circulation 02/2007; 115(4):442-9. · 15.20 Impact Factor
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    ABSTRACT: In this work we have combined biochemical and electrophysiological approaches to explore the modulation of rat ventricular transient outward K(+) current (I(to)) by calmodulin kinase II (CaMKII). Intracellular application of CaMKII inhibitors KN93, calmidazolium, and autocamtide-2-related inhibitory peptide II (ARIP-II) accelerated the inactivation of I(to), even at low [Ca(2+)]. In the same conditions, CaMKII coimmunoprecipitated with Kv4.3 channels, suggesting that phosphorylation of Kv4.3 channels modulate inactivation of I(to). Because channels underlying I(to) are heteromultimers of Kv4.2 and Kv4.3, we have explored the effect of CaMKII on human embryonic kidney (HEK) cells transfected with either of those Kvalpha-subunits. Whereas Kv4.3 inactivated faster upon inhibition of CaMKII, Kv4.2 inactivation was insensitive to CaMKII inhibitors. However, Kv4.2 inactivation became slower when high Ca(2+) was used in the pipette or when intracellular [Ca(2+)] ([Ca(2+)](i)) was transiently increased. This effect was inhibited by KN93, and Western blot analysis demonstrated Ca(2+)-dependent phosphorylation of Kv4.2 channels. On the contrary, CaMKII coimmunoprecipitated with Kv4.3 channels without a previous Ca(2+) increase, and the association was inhibited by KN93. These results suggest that both channels underlying I(to) are substrates of CaMKII, although with different sensitivities; Kv4.2 remain unphosphorylated unless [Ca(2+)](i) increases, whereas Kv4.3 are phosphorylated at rest. In addition to the functional impact that phosphorylation of Kv4 channels could cause on the shape of action potential, association of CaMKII with Kv4.3 provides a new role of Kv4.3 subunits as molecular scaffolds for concentrating CaMKII in the membrane, allowing Ca(2+)-dependent modulation by this enzyme of the associated Kv4.2 channels.
    AJP Heart and Circulatory Physiology 11/2006; 291(4):H1978-87. · 4.01 Impact Factor
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    ABSTRACT: Chlorpromazine (CPZ), a phenothiazine derivative, is a potent antipsychotic agent and imipramine (IP) is a widely used tricyclic antidepressant. The interaction between these molecules and erythrocyte membranes is of particular interest considering the role of these cells in the transport and release of these drugs at the central nervous system. In the present paper, we intend to study the effects of IP on erythrocyte membranes and to compare these effects with those of CPZ. Erythrocytes from adult Sprague-Dawley rats were incubated separately with different concentrations of IP or CPZ for lh at room temperature, fixed and stained by Giemsa. Changes in erythrocyte morphology were quantified by an image analysis system. The interaction of both drugs, CPZ and IP, with the erythrocyte membrane causes similar changes in cell shape. Increasing concentrations of both drugs induces the formation of stomatocytes, spherostomatocytes and spherocytes, because of an irreversible loss of area and volume, probably due to endovesiculation. Our results also show that the CPZ is more potent than IP.
    Journal of physiology and biochemistry 10/2006; 62(3):199-205. · 1.65 Impact Factor

Publication Stats

699 Citations
146.15 Total Impact Points

Institutions

  • 1992–2014
    • Universidad del País Vasco / Euskal Herriko Unibertsitatea
      • Departamento de Medicina
      Leioa, Basque Country, Spain
  • 1998–2012
    • Universidad de Colima
      • University Center for Biomedical Research
      Colima, Colima, Mexico
  • 2006–2007
    • University of Utah
      • Department of Physiology
      Salt Lake City, Utah, United States
    • Universidad de Valladolid
      • Departamento de Bioquímica y Biología Molecular y Fisiología
      Valladolid, Castile and Leon, Spain