Antonio Felipe

University of Barcelona | UB · Department of Biochemistry and Molecular Biology (Facultad de Biología)

Introduction: Kv1.3 is the main voltage-gated potassium channel of leukocytes from both the innate and adaptive immune systems. Channel function is required for common processes such as Ca2+ signaling but also for cell-specific events. In this context, alterations in Kv1.3 are associated with multiple immune disorders. Excessive channel activity c...

Aim The voltage‐gated Kv7.1 channel, in association with the regulatory subunit KCNE1, contributes to the I Ks current in the heart. However, both proteins travel to the plasma membrane using different routes. While KCNE1 follows a classical Golgi‐mediated anterograde pathway, Kv7.1 is located in endoplasmic reticulum‐plasma membrane junctions (ER‐...

Formation of the immunological synapse (IS) is a key event during initiation of an adaptive immune response to a specific antigen. During this process, a T cell and an Antigen Presenting Cell (APC) form a stable contact that allows the T cell to integrate both internal and external stimuli in order to decide whether to activate. The threshold for T...

Simple Summary The voltage-dependent potassium channel Kv1.3 is a potential target for cancer therapies. This channel exhibits a complex repertoire of physiological functions such as proliferation, activation, insulin sensitivity, nerve action potential and apoptosis among others. Furthermore, the expression and activity of Kv1.3 remodels in variou...

Protein lipidation is one of the most common forms of posttranslational modification. This alteration couples different lipids, such as fatty acids, phospho- and glycolipids and sterols, to cellular proteins. Lipidation regulates different aspects of the protein’s physiology, including structure, stability and affinity for cellular membranes and pr...

Members of the regulatory Kvβ family modulate the kinetics and traffic of voltage-dependent K+ (Kv) channels. The crystal structure of Kv channels associated with Kvβ peptides suggests a α4/β4 composition. Although Kvβ2 and Kvβ1 form heteromers, evidence supports that only Kvβ2.1 forms tetramers in the absence of α subunits. Therefore, the stoichio...

The voltage-dependent potassium (Kv) channel Kvβ family was the frst identifed group of modulators of Kv channels. Kvβ regulation of the α-subunits, in addition to their aldoketoreductase activity, has been under extensive study. However, scarce information about their specifc α-subunit-independent biology is available. The expression of Kvβs is...

Voltage-gated potassium channels control neuronal excitability and cardiac action potentials. In addition, these proteins are involved in a myriad of cellular processes. The potassium channel Kv1.3 plays an essential role in the immune response mediated by leukocytes. Kv1.3 is functional both at the plasma membrane and the inner mitochondrial membr...

The voltage-gated potassium channel Kv1.3 is a potential therapeutic target for obesity and diabetes. The genetic ablation and pharmacological inhibition of Kv1.3 lead to a lean phenotype in rodents. The mechanism of regulation of body weight and energy homeostasis involves Kv1.3 expression in different organs, including white and brown adipose tis...

The voltage-dependent potassium channel Kv1.3 plays essential roles in the immune system, participating in leukocyte activation, proliferation and apoptosis. The regulatory subunit KCNE4 acts as an ancillary peptide of Kv1.3, modulates K ⁺ currents and controls channel abundance at the cell surface. KCNE4-dependent regulation of the oligomeric comp...

The voltage-dependent potassium channel Kv1.3 participates in the immune response. Kv1.3 is essential in different cellular functions, such as proliferation, activation and apoptosis. Because aberrant expression of Kv1.3 is linked to autoimmune diseases, fine-tuning its function is crucial for leukocyte physiology. Regulatory KCNE subunits are expr...

The voltage-gated potassium channel Kv1.3 plays an apparent dual physiological role by participating in activation and proliferation of leukocytes as well as promoting apoptosis in several types of tumor cells. Therefore, Kv1.3 is considered a potential pharmacological target for immunodeficiency and cancer. Different cellular locations of Kv1.3, a...

Voltage-dependent potassium (Kv) channels contribute to the excitability of nerves and muscles. In addition, Kv participates in several cell functions, including cell cycle progression and proliferation. Kv channel remodeling has been associated with neoplastic cell growth and cancer. Kv7 channels are expressed in blood vessels, and they participat...

Ion channels (IChs) are transmembrane proteins that selectively drive ions across membranes. The function of IChs partially relies on their abundance and proper location in the cell, fine-tuned by the delicate balance between secretory, endocytic, and degradative pathways. The disruption of this balance is associated with several diseases, such as...

The voltage-gated potassium channel Kv1.3 plays a crucial role during the immune response. The channel forms oligomeric complexes by associating with several modulatory subunits. KCNE4, one of the five members of the KCNE family, binds to Kv1.3, altering channel activity and membrane expression. The association of KCNEs with Kv channels is the subj...

The potassium channel Kv7.1 associates with the KCNE1 regulatory subunit to trigger cardiac IKs currents. Although the Kv7.1/KCNE1 complex has received much attention, the subcellular compartment hosting the assembly is the subject of ongoing debate. Evidence suggests that the complex forms either earlier in the endoplasmic reticulum or directly at...

Confocal microscopy permits the analysis of the subcellular distribution of proteins. Colocalization between target proteins and specific markers of differential cell compartments provides an efficient approach to studying protein traffic. In this chapter, we describe an automated method to denoise confocal microscopy images and assess the colocali...

The voltage‐dependent potassium (Kv) channel Kv1.3 regulates leukocyte proliferation, activation, and apoptosis, and altered expression of this channel is linked to autoimmune diseases. Thus, the fine‐tuning of Kv1.3 function is crucial for the immune system response. The Kv1.3 accessory protein, potassium voltage‐gated channel subfamily E (KCNE) s...

Voltage-gated potassium channels (Kv) are the largest group of ion channels. Kv are involved in controlling the resting potential and action potential duration in the heart and brain. Additionally, these proteins participate in cell cycle progression as well as in several other important features in mammalian cell physiology, such as activation, di...

Rheumatoid arthritis (RA) is a serious autoimmune disease that has severe impacts on both the wellbeing of patients and the economy of the health system. Similar to many autoimmune diseases, RA concurs with a long evolution, which eventually results in highly debilitating symptoms. Therapeutic treatments last for long periods during RA. However, th...

Ion channels are transmembrane proteins that conduct specific ions across biological membranes. Ion channels are present at the onset of many cellular processes, and their malfunction triggers severe pathologies. Potassium channels (KChs) share a highly conserved signature that is necessary to conduct K+ through the pore region. To be functional, K...

The Spanish Ion Channel Initiative consortium (SICI, http://sici. [...]

The voltage-dependent potassium channel Kv1.3 participates in peripheral insulin sensitivity. Genetic ablation of Kv1.3 triggers resistance to diet-induced weight gain, thereby pointing to this protein as a pharmacological target for obesity and associated type II diabetes. However, this role is under intense debate because Kv1.3 expression in adip...

A KCNQ1 mutation, D242N, was found in a pair of twins and characterized at the cellular level. To investigate whether and how the mutation causes the clinically observed lost adaptation to fast heart rate, we performed a computational study. Firstly, we identified a new I Ks model based on voltage clamp experimental data. Then we included this form...

KV7.1 and KCNE1 co-assemble to give rise to the IKs current, one of the most important repolarizing currents of the cardiac action potential. Its relevance is underscored by the identification of > 500 mutations in KV7.1 and, at least, 36 in KCNE1, that cause Long QT Syndrome (LQTS). The aim of this study was to characterize the biophysical and cel...

The voltage-dependent potassium channel Kv1.3 plays essential physiological functions in the immune system. Kv1.3, regulating the membrane potential, facilitates downstream Ca²⁺ -dependent pathways and becomes concentrated in specific membrane microdomains that serve as signaling platforms. Increased and/or delocalized expression of the channel is...

The voltage-dependent potassium channel Kv1.3, playing crucial roles in leukocytes, physically interacts with KCNE4. This assembly inhibits the K(+) currents by retaining the channel within intracellular compartments. Thus KCNE subunits are novel regulators of K(+) channels in the immune system. Although the canonical interactions of KCNE with Kv7...

The adult mammalian brain contains neural stem cells (NSCs) that generate neurons and glial cells throughout the lifetime of an organism. NSCs reside in at least two germinal epithelium regions of the adult brain, the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the hippocampus. Newborn neurons incorporate into th...

The potassium channel Kv1.3 plays roles in immunity, neuronal development and sensory discrimination. Regulation of Kv1.3 by kinase signaling has been studied. In this context, EGF binds to specific receptors (EGFR) and triggers tyrosine kinase-dependent signaling, which down-regulates Kv1.3 currents. We show that Kv1.3 undergoes EGF-dependent endo...

The spatial localization of ion channels at the cell surface is crucial for their functional role. Many channels localize in lipid raft microdomains, which are enriched in cholesterol and sphingolipids. Caveolae, specific lipid rafts which concentrate caveolins, harbor signaling molecules and their targets becoming signaling platforms crucial in ce...

Introduction: The voltage-dependent potassium channel Kv1.3 is mainly present in the nervous and immune systems. In leukocytes, Kv1.3 fine-tunes the activation and proliferation of the immune response. However, Kv1.3 is also present in other tissues where its physiological role is still under investigation. Thus, Kv1.3 alterations have been relate...

Aims: KCNQ1 and KCNE1 encode Kv7.1 and KCNE1, respectively, the pore-forming and the accessory subunits of the slow delayed rectifier potassium current, IKs. KCNQ1 mutations are associated with long and short QT syndrome. The aim of this study was to characterize the biophysical and cellular phenotype of a KCNQ1 missense mutation, F279I, found in...

Calmodulin (CaM) binding to the AB module is critical for multiple mechanisms governing the function of Kv7.2 potassium subunits, which are one of the main components of the non-inactivating K(+) M-current, a key controller of neuronal excitability. Structural analysis indicates that the CaM N-lobe engages with helix B, whereas the C-lobe anchors t...

AIMS: Polyunsaturated fatty n-3 acids (PUFAs) have been reported to exhibit antiarrhythmic properties. However, the mechanisms of action remain unclear. We studied the electrophysiological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on IKs, and on the expression and location of Kv7.1 and KCNE1. METHODS AND RESULTS: Experim...

Potassium channels are a diverse group of pore-forming transmembrane proteins that selectively facilitate potassium flow through an electrochemical gradient. They participate in the control of the membrane potential and cell excitability in addition to different cell functions such as cell volume regulation, proliferation, cell migration, angiogene...

Introduction: The Kv1.3 channel is crucial in sensory neurons and leukocytes. The anterograde transport and membrane expression of Kv1.3 is altered in autoimmune diseases and deficient axonal targeting.Unexpectedly, molecular mechanisms underlying Kv1.3 channel trafficking remain elusive. Materials and Methods: We studied the role of the Kv1.3 C-te...

Objective: Voltage-dependent K(+) (Kv) channels from the Kv7 family are expressed in blood vessels and contribute to cardiovascular physiology. Although Kv7 channel blockers trigger muscle contractions, Kv7 activators act as vasorelaxants. Kv7.1 and Kv7.5 are expressed in many vessels. Kv7.1 is under intense investigation because Kv7.1 blockers fa...

The outcome of a malignant disease depends on the efficacy of the immune system to destroy cancer cells. Key steps in this process, for example the generation of a proper Ca(2+) signal induced by recognition of a specific antigen, are regulated by various ion channel including voltage-gated Kv1.3 and Ca(2+)-activated KCa3.1 K(+) channels, and the i...

Impairment of Kv1.3 membrane expression in leukocytes and sensory neuron contributes to the pathophysiology of autoimmune diseases and sensory syndromes. Molecular mechanisms underlying Kv1.3 channel trafficking to the plasma membrane remain elusive. We report a novel non-canonical di-acidic signal (E(483/484)) at the C-terminus of Kv1.3 essential...

Voltage-dependent K⁺ channels (Kv) are involved in a number of physiological processes, including immunomodulation, cell volume regulation, apoptosis as well as differentiation. Some Kv channels participate in the proliferation and migration of normal and tumor cells, contributing to metastasis. Altered expression of Kv1.3 and Kv1.5 channels has be...

Kv, which play a role in the immune system, are remodeled during carcinogenesis. Leukocytes present a limited Kv repertoire, with Kv1.3 and Kv1.5 as isoforms that are involved in neoplastic processes, such as proliferation and migration. In this study, we identified Kv1.5 in B-lymphocytes, characterized its role in proliferation and migration, and...

Voltage-dependent K (+) (Kv) channels are tightly regulated during the immune system response. Leukocytes have a limited repertoire of Kv channels, whose physiological role is under intense investigation. A functional Kv channel is an oligomeric complex composed of pore-forming and ancillary subunits. The KCNE gene family is a novel group of modula...

Voltage-dependent K(+) channels (Kv) are involved in the proliferation and differentiation of mammalian cells, since Kv antagonists impair cell cycle progression. Although myofibers are terminally differentiated, some myoblasts may re-enter the cell cycle and proliferate. Since Kv1.3 and Kv1.5 expression is remodeled during tumorigenesis and is inv...

Potassium Channels in the Immune System Regulation of Potassium Channels by Membrane Cholesterol and Lipid Raft Microdomains Localization of Major Voltage-Dependent Kv1.3 and Kv1.5 Channels in Cholesterol-Rich Membrane Microdomains in Leukocytes Mechanisms of Ion Channel Regulation: The Immunological Synapse Acknowledgments References

Kv1.5 channels are the primary channels contributing to the ultrarapid outward potassium current (IKur). The regulatory Kvβ1.3 subunit converts Kv1.5 channels from delayed rectifiers with a modest degree of slow inactivation to channels with both fast and slow inactivation components. Previous studies have shown that inhibition of PKC with calphost...

Because Kv1.3 and Kv1.5 K(+) channels are remodeled during tumorigenesis and participate in skeletal muscle proliferation, we analyzed their expression in human skeletal muscle sarcomas. Aggressive alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) were studied. Kv1.5 expression was moderate in adult muscle and low in ERMS, wher...

Kv7 (KCNQ) proteins form a family of voltage-gated potassium channels that is comprised of five members, Kv7.1-Kv7.5. While Kv7.1 is crucial in the heart, the Kv7.2-Kv7.5 channels contribute to the M-current in the nervous system. In addition, Kv7.5 is expressed in muscles, where its physiological role is currently under evaluation. Kv7 association...

Kv7.5 (KCNQ5) channels conduct M-type potassium currents in the brain, are expressed in skeletal muscle, and contribute to vascular muscle tone. We coexpressed Kv7.5 and KCNE1-3 peptides in HEK293 cells and then analyzed their association using electrophysiology and co-immunoprecipitation, assessed localization using confocal microscopy, examined t...

Potassium channels (KCh) are a diverse group of membrane proteins that participate in the control of the membrane potential. More than eighty different KCh genes have been identified, which are expressed in virtually all living cells. In addition to nerve and cardiac action potentials, these proteins are involved in a number of physiological proces...

The KCNQ1 (Kv7.1) channel plays an important role in cardiovascular physiology. Cardiomyocytes co-express KCNQ1 with KCNE1-5 proteins. KCNQ1 may co-associate with multiple KCNE regulatory subunits to generate different biophysically and pharmacologically distinct channels. Increasing evidence indicates that the location and targeting of channels ar...

For the last 20 years, knowledge of the physiological role of voltage-dependent potassium channels (Kv) in the immune system has grown exponentially. Leukocytes express a limited repertoire of Kv channels, which contribute to the membrane potential. These proteins are involved in the immune response and are therefore considered good pharmacological...

Kv1.3 plays a crucial role in the activation and proliferation of T-lymphocytes and macrophages. While Kv1.3 is responsible for the voltage-dependent potassium current in T-cells, in macrophages this K(+) current is generated by the association of Kv1.3 and Kv1.5. Patients with autoimmune diseases show a high number of effector memory T cells that...

Voltage-dependent K(+) channels (Kv) control repolarization and membrane potential in electrically excitable cells. In addition, Kv channels are involved in the maintenance of vascular smooth muscle tone, insulin release, epithelial K(+) transport, cell proliferation and leukocyte activation. Kv1.3 and Kv1.5 are widely distributed throughout the bo...

The study of channel modulation by regulatory subunits has attracted considerable attention. Evidence indicates a pivotal role for accessory proteins in the channelosome. For instance, these regulatory subunits are necessary to recapitulate in vivo ion currents and to further understand the physiological role of ion channels. KCNEs are a family of...

Voltage-dependent potassium (K(v)) channels play a pivotal role in the modulation of macrophage physiology. Macrophages are professional antigen-presenting cells and produce inflammatory and immunoactive substances that modulate the immune response. Blockage of K(v) channels by specific antagonists decreases macrophage cytokine production and inhib...

Voltage-dependent potassium channels play a pivotal role in the modulation of macrophage physiology. Macrophages are professional antigen-presenting cells and produce inflammatory and immunoactive substances that modulate the immune response. Blockage of Kv channels by specific antagonists decreases macrophage cytokine production and inhibits proli...

Membrane ion channels participate in cancerous processes such as proliferation, migration and invasion, which contribute to metastasis. Increasing evidence indicates that voltage-dependent K+ (Kv) channels are involved in the proliferation of many types of cells, including tumor cells. Kv channels have generated immense interest as a promising tool...

Kv7 (KCNQ) proteins form a family of voltage-gated potassium channels that is comprised of five members, Kv7.1-Kv7.5. While Kv7.1 is crucial in the heart, the Kv7.2, Kv7.3, Kv7.4 and Kv7.5 channels contribute to the M-current in the nervous system. In addition to the brain, Kv7.5 is expressed in skeletal and smooth muscle, where its physiological r...

Modulation of the expression and activity of plasma membrane ion channels is one of the mechanisms by which immune cells can regulate their intracellular Ca(2+) signaling pathways required for proliferation and/or differentiation. Voltage-gated K+ channels, inwardly rectifying K+ channels, and Ca(2+)-activated K+ channels have been described to pla...

Voltage-dependent potassium channels (Kv) play a crucial role in the activation and proliferation of leukocytes. Kv channels are either homo- or hetero-oligomers. This composition modulates their surface expression and serves as a mechanism for regulating channel activity. Kv channel interaction with accessory subunits provides mechanisms for chann...

Surface expression of voltage-dependent K+ channels (Kv) has a pivotal role in leukocyte physiology. Although little is known about the physiological role of lipid rafts, these microdomains concentrate signaling molecules and their ion channel substrates. Kv1.3 associates with Kv1.5 to form functional channels in macrophages. Different isoform stoi...

Voltage-gated sodium channels (Nav) consist of a pore-forming alpha subunit (Navα) associated with beta regulatory subunits (Navβ). Adult skeletal myocytes primarily express Nav1.4 channels. We found, however, using neonatal L6E9 myocytes, that myofibers acquire a Nav1.5-cardiac-like phenotype efficiently. Differentiated myotubes elicited faster Na...

Surface expression of voltage-dependent K(+) channels (Kv) has a pivotal role in leukocyte physiology. Although little is known about the physiological role of lipid rafts, these microdomains concentrate signaling molecules and their ion channel substrates. Kv1.3 associates with Kv1.5 to form functional channels in macrophages. Different isoform st...

Potassium channels, which are essential to a wide range of physiological processes, are involved in many diseases. Thus, alterations in such important proteins due to congenital deficiencies or to undesirable side-effects of common medications might lead to dysfunctions. Heart is one of those tissues where potassium channels play a crucial role. Th...

Voltage-dependent K(+) channels (Kv) are involved in myocyte proliferation and differentiation by triggering changes in membrane potential and regulating cell volume. Since Kv7 channels may participate in these events, the purpose of this study was to investigate whether skeletal muscle Kv7.1 and Kv7.5 were involved during proliferation and myogene...

Voltage-dependent K(+) channels (Kv) are involved in the proliferation of many types of cells, but the mechanisms by which their activity is related to cell growth remain unclear. Kv antagonists inhibit the proliferation of mammalian cells, which is of physiological relevance in skeletal muscle. Although myofibres are terminally differentiated, som...

Voltage-gated sodium channels (Nav) consist of a pore-forming α subunit (Navα) associated with β regulatory subunits (Navβ). Adult skeletal myocytes primarily express Nav1.4 channels. We found, however, using neonatal L6E9 myocytes, that myofibers acquire a Nav1.5-cardiac-like phenotype efficiently. Differentiated myotubes elicited faster Nav1.5 cu...

Kv1.3 activity is determined by raft association. In addition to Kv1.3, leukocytes also express Kv1.5, and both channels control physiological responses. Because the oligomeric composition may modify the channel targeting to the membrane, we investigated heterotetrameric Kv1.3/Kv1.5 channel traffic and targeting in HEK cells. Kv1.3 and Kv1.5 genera...