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At least 19 recordsLinked to original sources
PubMed2005

Disease-associated changes in the expression of ion channels, ion receptors, ion exchangers and Ca(2+)-handling proteins in heart hypertrophy.

The molecular pathology of cardiac hypertrophy is multifactorial with transcript regulation of ion channels, ion exchangers and Ca(2+)-handling proteins being speculative. We therefore investigated disease-associated changes in gene expression of various ion channels and their receptors as well as ion exchangers, cytoskeletal proteins and Ca(2+)-handling proteins in normotensive and spontaneously hypertensive (SHR) rats. We also compared experimental findings with results from hypertrophic human hearts, previously published (Borlak, J., and Thum, T., 2003. Hallmarks of ion channel gene expression in end-stage heart failure. FASEB J. 17, 1592-1608). We observed significant (P < 0.05) induction in transcript level of ATP-driven ion exchangers (Atp1A1, NCX-1, SERCA2a), ion channels (L-type Ca(2+)-channel, K(ir)3.4, Na(v)1.5) and RyR-2 in hypertrophic hearts, while gene expression was repressed in diseased human hearts. Further, the genes coding for calreticulin and calmodulin, PMCA 1 and 4 as well as alpha-skeletal actin were significantly (P < 0.05) changed in hypertrophic human heart, but were unchanged in hypertrophic left ventricles of the rat heart. Notably, transcript level of alpha- and beta-MHC, calsequestrin, K(ir)6.1 (in the right ventricle only), phospholamban as well as troponin T were repressed in both diseased human and rat hearts. Our study enabled an identification of disease-associated candidate genes. Their regulation is likely to be the result of an imbalance between pressure load/stretch force and vascular tonus and the observed changes may provide a rational for the rhythm disturbances observed in patients with cardiac hypertrophy.

Animals↗
PubMed2003

HLM1, an essential signaling component in the hypersensitive response, is a member of the cyclic nucleotide-gated channel ion channel family.

The hypersensitive response (HR) in plants is a programmed cell death that is commonly associated with disease resistance. A novel mutation in Arabidopsis, hlm1, which causes aberrant regulation of cell death, manifested by a lesion-mimic phenotype and an altered HR, segregated as a single recessive allele. Broad-spectrum defense mechanisms remained functional or were constitutive in the mutant plants, which also exhibited increased resistance to a virulent strain of Pseudomonas syringae pv tomato. In response to avirulent strains of the same pathogen, the hlm1 mutant showed differential abilities to restrict bacterial growth, depending on the avirulence gene expressed by the pathogen. The HLM1 gene encodes a cyclic nucleotide-gated channel, CNGC4. Preliminary study of the HLM1/CNGC4 gene pro-duct in Xenopus oocytes (inside-out patch-clamp technique) showed that CNGC4 is permeable to both K(+) and Na(+) and is activated by both cGMP and cAMP. HLM1 gene expression is induced in response to pathogen infection and some pathogen-related signals. Thus, HLM1 might constitute a common downstream component of the signaling pathways leading to HR/resistance.

Alleles↗
PubMed1996

Effects of ethanol on ion channels.

Ion channels play critical roles in nervous system function, from initiating rapid synaptic activity to propagation of action potentials. Studies have indicated that many of the effects of ethanol on the nervous system are likely caused by the actions of ethanol on ion channels. Ion channels are multimeric structures that gate ions through subtle changes in tertiary structure. Ethanol readily enters molecular sites within multimeric ion channels, modifying intermolecular forces and bonds that are important for the open-close-inactivation kinetic properties of channels. The diversity of channel composition caused by the multimeric structure results in subtypes of channels that have a spectrum of sensitivity to ethanol that translates into brain regional differences in ethanol sensitivity, in part caused by differences in ion channel subunit composition. Ethanol has been shown to affect both receptor-activated ion channels and voltage-gated ion channels. The acute intoxicating and incoordinating effects of ethanol are probably related to inhibition of subtypes of NMDA-glutamate receptor ion channels and potentiation of certain subtypes of GABAA receptor ion channels. Effects on these channels, as well as glycine, nicotinic cholinergic, serotonergic, and other ion channels, likely contribute to the euphoric, sedative, and other acute actions of ethanol. Changes in ion channel subunit composition, density, and properties probably also contribute to ethanol tolerance, dependence, withdrawal hyperexcitability, and neurotoxicity. A substantial number of studies have implicated glutamate NMDA receptor, GABAA, and L-type voltage-gated calcium channels in the adaptive changes in the brain during chronic ethanol exposure. The diversity of ion channels subunits, their prominent role in brain function, and ethanol action are likely to make them important contributors to alcoholism and alcohol abuse.

Animals↗
PubMed1990

Memory is a property of an ion channels pool: ion channels formed by Staphylococcus aureus alpha-toxin.

The short-time depolarization effects on the integral conductance induced by S. aureus alpha-toxin (ST) in planar lipid bilayer membranes has been studied. Ion channels formed by ST were found to have several potential-induced nonconductance (closed) states. The transitions of ion channels between the states are only through one conductance state. The transition of ST-channels from closed to open state is induced by membrane depolarization. The amplitude current after a series of voltage pulses is a function of pulse number, and is effectively independent of the time interval between the neighbouring pulses. Therefore, a membrane which contains a pool of ion channels "remembers" its previous existence. A simple model can be used to explain this phenomenon.

Bacterial Toxins↗
PubMed2006

[Mitochondrial ion channels].

Ion channels are proteins, which facilitate the ions flow throught biological membranes. In recent years the structure as well as the function of the plasma membrane ion channels have been well investigated. The knowledge of intracellular ion channels however is still poor. Up till now, the calcium channel described in endoplasmatic reticulum and mitochondrial porine are the examples of intracellular ion channels, which have been well characterized. The mitochondrial potassium channels: regulated by ATP (mitoK(ATP)) and of big conductance activated by Ca2+ (mitoBK(Ca)), which were described in inner mitochondrial membrane, play a key role in the protection of heart muscle against ischemia. In this review the last date concerning the mitochondrial ion channels as well as they function in cell metabolism have been presented.

Adenosine Triphosphate↗
PubMed1997

Diseases caused by voltage-gated ion channels.

Ion channels regulate the transfer of ions between the outer and the inner surface of the cell membrane. The opening of ion channels may be triggered by the binding of a ligand or variations in the membrane potential. Voltage-gated ion channels are an important class of such channels, that are involved in the generation and propagation of action potentials and play a key role in cell to cell communication. As a consequence of cloning and sequencing of ion channel genes, their role in diseases affecting excitable tissues such as the nervous system, heart and skeletal muscle has been examined, and a new class of diseases has emerged. We will review disorders caused by mutations in voltage-gated ion channels affecting these excitable tissues as well as non-excitable tissues such as the kidney. The clinician should be aware of this new class of diseases because pharmacological agents modulating channel functions are available. Characterization of these gene defects should lead to better treatment of these disorders.

Animals↗
PubMed2002

Surface potentials and the calculated selectivity of ion channels.

Ion channels catalyze the transport of ions across biological membranes. A proper understanding of ion-channel functioning is essential to our knowledge of cell physiology, and, in this context, ion-channel selectivity is a key concept. The extent to which a channel permeates two ion species, a and b, is expressed by the permeability ratio, P(a)/P(b). This paper addresses a complication in the calculation of P(a)/P(b) that is related to the existence of surface potentials (psi) and that so far has not been fully appreciated. This paper shows the rather surprising effect of psi on the calculated P(a)/P(b) of a channel that is permeable to two ion species of different valence. If we ignore psi, we conclude, for instance, P(a) > P(b). If we implement psi in the calculation of P(a)/P(b), we may, however, conclude exactly the reverse, i.e., P(a) < P(b). Because electrostatic potentials arise at the surface of essentially all biological membranes, this paper argues for a more critical evaluation of ion channel selectivity measurements.

Biological Transport↗
PubMed2006

Probing the effects of phosphoinositides on ion channels.

Ion channels are integral membrane proteins that control transmembrane ion fluxes to regulate membrane potential, cell excitability, and ion transport. Membrane phospholipids containing phosphoinositides have recently emerged as important regulators of many ion channels, including inward rectifier K+ channel, voltage-gated K+ and Ca2+ channels, transient receptor potential channels, and intracellular inositol-1,4,5-trisphosphate receptor ion channels. Discussed here are several methods for studying regulation of ion channels by phospholipids.

Animals↗
PubMed2002

Genetic disorders of neuromuscular ion channels.

Ion channels are complex proteins that span the lipid bilayer of the cell membrane, where they orchestrate the electrical signals necessary for normal function of the central nervous system, peripheral nerve, and both skeletal and cardiac muscle. The role of ion channel defects in the pathogenesis of numerous disorders, many of them neuromuscular, has become increasingly apparent over the last decade. Progress in molecular biology has allowed cloning and expression of genes that encode channel proteins, while comparable advances in biophysics, including patch-clamp electrophysiology and related techniques, have made the study of expressed proteins at the level of single channel molecules possible. Understanding the molecular basis of ion channel function and dysfunction will facilitate both the accurate classification of these disorders and the rational development of specific therapeutic interventions. This review encompasses clinical, genetic, and pathophysiological aspects of ion channels disorders, focusing mainly on those with neuromuscular manifestations.

Humans↗
PubMed2002

Genome-wide detection and family clustering of ion channels.

Ion channels represent an important class of molecules that can be classified into 13 distinct groups. We present a strategy using a "learning set" of well-annotated ion channel sequences to detect homologues in 32 entire genome sequences from Archaea, Bacteria and Eukarya. A total of 299 putative ion channel protein sequences were detected, with significant variations across species. The clustering of these sequences reveals complex relationships between the different ion channel families.

Archaeal Proteins↗
PubMed2005

Pharmacogenetics and cardiac ion channels.

Ion channels control electrical excitability in living cells. In mammalian heart, the opposing actions of Na(+) and Ca(2+) ion influx, and K(+) ion efflux, through cardiac ion channels determine the morphology and duration of action potentials in cardiac myocytes, thus controlling the heartbeat. The last decade has seen a leap in our understanding of the molecular genetic origins of inherited cardiac arrhythmia, largely through identification of mutations in cardiac ion channels and the proteins that regulate them. Further, recent advances have shown that 'acquired arrhythmias', which occur more commonly than inherited arrhythmias, arise due to a variety of environmental factors including side effects of therapeutic drugs and often have a significant genetic component. Here, we review the pharmacogenetics of cardiac ion channels-the interplay between genetic and pharmacological factors that underlie human cardiac arrhythmias.

Anti-Arrhythmia Agents↗
PubMed1993

Membrane ion channels and cardiovascular ATP-sensitive K+ channels.

Ion channels are the primary target for a variety of clinically important drugs including local anesthetic, antihypertensive, antianginal, antiarrhythmic, antidiabetic, anticonvulsant hypnotic and anxiolytic agents. Ion channels are specialized proteins inserted in the ion-impermeable cellular membrane, which have a water-filled pore permitting the selective passage of a few biologically important ions (Na+, K+, Ca++ and Cl-) across the membrane. Multiple channels for a given ion can co-exist on the same cell where they have specific functions. The flow of ions through channels produces electrical currents which often act as biological messengers to change and modulate the functional state of the cell. Thus, the influx of Na+ and Ca++ are activating signals whereas the exit of K+ drives the activated cell to a resting state or strengthen the resting state. Interestingly, K+ channels are the most diverse group of ion channels. At least 9 families of K+ channels co-exist in cardiac myocytes where they regulate the heart repolarization and excitability processes under physiological and pathological conditions. ATP-sensitive K+ channels of cardiac myocytes are of particular interest since they have a very high membrane density and are closed under normoxic conditions, becoming operational during ischemic stress when the intracellular levels of ATP decline. Their major function has been proposed to be the preservation of viability of the myocyte during ischemia. ATP-sensitive K+ channels are also present in other tissues, such as the blood vessels, where their opening causes strong relaxing effects. Cardiac and vascular ATP-sensitive K+ channels are the primary target of a novel class of drugs, called K+ channel openers, such as nicorandil and aprikalim.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1999

Disorders of neuromuscular junction ion channels.

Ion channel defects produce a clinically diverse set of disorders that range from cystic fibrosis and some forms of migraine to renal tubular defects and episodic ataxias. This review discusses diseases related to impaired function of the skeletal muscle acetylcholine receptor and calcium channels of the motor nerve terminal. Myasthenia gravis is an autoimmune disease caused by antibodies directed toward the skeletal muscle acetylcholine receptor that compromise neuromuscular transmission. Congenital myasthenias are genetic disorders, a subset of which are caused by mutations of the acetylcholine receptor. Lambert-Eaton myasthenic syndrome is an immune disorder characterized by impaired synaptic vesicle release likely related to a defect of calcium influx. The disorders will illustrate new insights into synaptic transmission and ion channel structure that are relevant for all ion channel disorders.

Acetylcholine↗
PubMed2002

Can electromagnetic radiations induce changes in the kinetics of voltage-dependent ion channels?

Ion channels are protein molecules, which can assume distinct open and closed conformational states, a phenomenon termed ion channel kinetics. The transitions from one state to another depend on the potential energy barrier that separates those two states. Therefore, it is rational to suppose that electromagnetic waves could interact with this barrier and induce changes in the rate transitions of this kinetic process. Our aim is to answer the question: can electromagnetic radiations induce changes in the kinetics of voltage-dependent ion channels? We simulated the effects of the low and high frequency electromagnetic waves on the sodium and potassium channels of the giant axon of Loligo. The key parameter measured was the fractional open time (fv), because it reflects the voltage dependence of the kinetics of channels. The electromagnetic radiations induced the following changes in the kinetics of the potassium and sodium channels: i/ low frequency waves kept the potassium channel 50% of the time open independent on the mean voltage applied through the membrane; ii/ a gradual inhibition of the inactivation on the sodium channel, when the amplitudes of the low frequency waves were increased; iii/ high frequency waves on the potassium channel, decreased both Vo (voltage in which the channel stays 50% open) and the steepness of fv (d fv/dV) as the amplitudes of the waves increased, and iv/ high frequency and low amplitude radiations on the sodium channel decreased the maximum value of fv (in relation to control), while high amplitudes increased this value. In conclusion, high and low frequency electromagnetic radiations were able to change the kinetics of the potassium and sodium channels in a squid giant axon model.

Animals↗
PubMed1988

Synthetic amphiphilic peptide models for protein ion channels.

Ion channel proteins are important for the conduction of ions across biological membranes. Recent analyses of their sequences have suggested that they are composed of bundles of alpha-helices that associate to form ion-conducting channels. To gain insight into the mechanisms by which alpha-helices can aggregate and conduct ions, three model peptides containing only leucine and serine residues were synthesized and characterized. A 21-residue peptide, H2N-(Leu-Ser-Ser-Leu-Leu-Ser-Leu)3-CONH2, which was designed to be a membrane-spanning amphiphilic alpha-helix, formed well-defined ion channels with ion permeability and lifetime characteristics resembling the acetylcholine receptor. In contrast, a 14-residue version of this peptide, which was too short to span the phospolipid bilayer as an alpha-helix, failed to form discrete, stable channels. A third peptide, H2N-(Leu-Ser-Leu-Leu-Leu-Ser-Leu)3-CONH2, in which one serine per heptad repeat was replaced by leucine, produced proton-selective channels. Computer graphics and energy minimization were used to create molecular models that were consistent with the observed properties of the channels.

Computer Graphics↗
PubMed1988

Regulation of renal ion channels.

Ion channels in renal epithelia are involved in maintenance of the volume and ion composition of the epithelial cells themselves and of the entire organism. The latter function depends on transepithelial ion transport, a process that often involves ion channels at the apical (luminal) and/or the basolateral (contraluminal) cell membranes. Regulation of these channels is accomplished within many different time frames, each of which can involve different molecular mechanisms of regulation. Changes in membrane voltage, intracellular ion composition, or mechanical force on the membrane mediate short-term regulation. Biosynthesis, degradation, and reversible transfer of channels to or from cytoplasmic stores are responsible for longer term regulation. Covalent modification of channel proteins can be involved in either short- or long-term regulation. In this review we outline the different models of ion channel regulation in renal epithelia and give examples that emphasize the physiological roles of these channels in specific nephron segments.

Animals↗
PubMed2006

Engineering light-gated ion channels.

Ion channels are gated by a variety of stimuli, including ligands, voltage, membrane tension, temperature, and even light. Natural gates can be altered and augmented using synthetic chemistry and molecular biology to develop channels with completely new functional properties. Light-sensitive channels are particularly attractive because optical manipulation offers a high degree of spatial and temporal control. Over the last few decades, several channels have been successfully rendered responsive to light, including the nicotinic acetylcholine receptor, gramicidin A, a voltage-gated potassium channel, an ionotropic glutamate receptor, alpha-hemolysin, and a mechanosensitive channel. Very recently, naturally occurring light-gated cation channels have been discovered. This review covers the molecular principles that guide the engineering of light-gated ion channels for applications in biology and medicine.

Animals↗