Stretch-inactivated ion channels coexist with stretch-activated ion channels

Stretch-activated ion channels of animal, plant, bacterial, and fungal cells are implicated in mechanotransduction and osmoregulation. A new class of channel has now been described that is stretch-inactivated. These channels occur in neurons, where they coexist with stretch-activated channels. Both channels are potassium selective. The differing stretch sensitivities of the two channels minimize potassium conductance over an intermediate range of tension, with the consequence that, over this same range, voltage-gated calcium channels are most readily opened. Thus, by setting the relation between membrane tension and transmembrane calcium fluxes, stretch-sensitive potassium channels may participate in the control of calcium-dependent motility in differentiating, regenerating, or migrating neurons.     

Biophysical studies of ion channels

Ionic channels, the integral membrane proteins responsible for the brain's electrical activity, have long been studied with standard electrophysiological and biochemical methods. Recently, however, newly developed electrical and molecular biological methods have been brought to bear on long-standing questions in neurobiology. Goals of current channel research include elucidating the primary amino acid sequence and three-dimensional structure of channel species; the mechanisms of synthesis, sorting, membrane insertion, and degradation; and aspects of function such as gating, ion permeation and selectivity, and regulation. The latest research combines the new biochemical and electrophysiological techniques to reveal relations between molecular structure and function.     

Principles of selective ion transport in channels and pumps

The transport of ions across the membranes of cells and organelles is a prerequisite for many of life's processes. Transport often involves very precise selectivity for specific ions. Recently, atomic-resolution structures have been determined for channels or pumps that are selective for sodium, potassium, calcium, and chloride: four of the most abundant ions in biology. From these structures we can begin to understand the principles of selective ion transport in terms of the architecture and detailed chemistry of the ion conduction pathways.     

Multiple calcium channels and neuronal function

Recent investigations have demonstrated that neurons have a number of different types of calcium channels, each with their own unique properties and pharmacology. These calcium channels may be important in the control of different aspects of nerve activity. Some of the possibilities can now be discussed.     

植物根细胞离子通道研究进展

根细胞膜上存在各种离子通道.电生理学的研究表明,根细胞离子通道对于矿质吸收、转运及植物耐盐具有重要作用.该文概述了根细胞K+通道、阴离子通道和各种非选择性阳离子通道的最新研究进展,并对近期有关离子通道和植物耐盐性关系的研究进行了总结.K+通道存在于大多数的植物细胞中,其对K+的选择性远高于其他阳离子,K+通道的存在对于营养元素的吸收,尤其是K+的低亲和性吸收具有重要的意义,同时也为其他离子的出入维持了一个较为稳定的膜电势.阴离子通道激活所引起的质膜去极化可以激发非选择性的阳离子流,在盐胁迫下,可通透Cl的阴离子通道的开放是植物对胞内Cl的一种重要调控机制.由于非选择性的阳离子通道(Non-selective cation channels,NSCCs)的多样性及其对一价阳离子的低选择性,近年来NSCCs的研究受到广泛关注.NSCCs被认为参与了植物多种生理过程,包括营养元素的吸收、膨压控制、胞间转运、信号转导以及毒害离子的吸收,尤其是Na+的吸收.      

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.     

Organization of ion channels in the myelinated nerve fiber

The functional organization of the mammalian myelinated nerve fiber is complex and elegant. In contrast to nonmyelinated axons, whose membranes have a relatively uniform structure, the mammalian myelinated axon exhibits a high degree of regional specialization that extends to the location of voltage-dependent ion channels within the axon membrane. Sodium and potassium channels are segregated into complementary membrane domains, with a distribution reflecting that of the overlying Schwann or glial cells. This complexity of organization has important implications for physiology and pathophysiology, particularly with respect to the development of myelinated fibers.     

Mitogens and oncogenes can block the induction of specific voltage-gated ion channels

The mechanisms underlying the ontogeny of voltage-gated ion channels in muscle are unknown. Whether expression of voltage-gated channels is dependent on mitogen withdrawal and growth arrest, as is generally true for the induction of muscle-specific gene products, was investigated in the BC3H1 muscle cell line by patch-clamp techniques. Differentiated BC3H1 myocytes expressed functional Ca2+ and Na+ channels that correspond to those found in T tubules of skeletal muscle. However, Ca2+ and Na+ channels were first detected after about 5 days of mitogen withdrawal. In order to test whether cellular oncogenes, as surrogates for exogenous growth factors, could prevent the expression of ion channels whose induction was contingent on mitogen withdrawal, BC3H1 cells were modified by stable transfection with oncogene expression vectors. Expression vectors containing v-erbB, or c-myc under the control of the SV40 promoter, delayed but did not prevent the appearance of functional Ca2+ and Na+ channels. In contrast, transfection with a Val12 c-H-ras vector, or cotransfection of c-myc together with v-erbB, suppressed the formation of functional Ca2+ and Na+ channels for greater than or equal to 4 weeks. Potassium channels were affected neither by mitogenic medium nor by transfected oncogenes. Thus, the selective effects of certain oncogenes on ion channel induction corresponded to the suppressive effects of mitogenic medium.     

Mutations affecting TEA blockade and ion permeation in voltage-activated K+ channels

Voltage-dependent ion channels are responsible for electrical signaling in neurons and other cells. The main classes of voltage-dependent channels (sodium-, calcium-, and potassium-selective channels) have closely related molecular structures. For one member of this superfamily, the transiently voltage-activated Shaker H4 potassium channel, specific amino acid residues have now been identified that affect channel blockade by the small ion tetraethylammonium, as well as the conduction of ions through the pore. Furthermore, variation at one of these amino acid positions among naturally occurring potassium channels may account for most of their differences in sensitivity to tetraethylammonium.     

The coupling of neurotransmitter receptors to ion channels in the brain

Recent studies on the action of neurotransmitters on hippocampal pyramidal cells indicate that different neurotransmitter receptors that use either the same or different coupling mechanisms converge onto the same ion channel. Conversely, virtually all of the neurotransmitters act on at least two distinct receptor subtypes coupled to different ion channels on the same cell. The existence of both convergence and divergence in the action of neurotransmitters results in a remarkable diversity in neuronal signaling.     

Increased numbers of ion channels promoted by an intracellular second messenger

The anomalous rectifier potassium current in Aplysia neurons was examined to determine the immediate cause of an increase in conductance induced by serotonin and mediated by adenosine 3',5'-monophosphate. Voltage-dependent cesium ion block and steady-state current power spectral density were measured under voltage clamp before and after application of serotonin. The amplitude of the anomalous rectifier conductance was increased by adding serotonin, but the shapes of the conductance-voltage curve and the power spectrum were not altered. Calculation of the number of functional channels and of the single-channel conductance from the power spectra indicates that the serotonin-induced increase in conductance resulted from an increase in the number of functional channels, while the single-channel conductance and the open-channel probability were unchanged.     

Stereospecific effects of inhalational general anesthetic optical isomers on nerve ion channels

Although it is generally agreed that general anesthetics ultimately act on neuronal ion channels, there is considerable controversy over whether this occurs by direct binding to protein or secondarily by nonspecific perturbation of lipids. Very pure optical isomers of the inhalational general anesthetic isoflurane exhibited clear stereoselectivity in their effects on particularly sensitive ion channels in identified molluscan central nervous system neurons. At the human median effect dose (ED50) for general anesthesia, the (+)-isomer was about twofold more effective than the (-)-isomer both in eliciting the anesthetic-activated potassium current IK(An) and in inhibiting a current mediated by neuronal nicotinic acetylcholine receptors. For inhibiting the much less sensitive transient potassium current IA, the (-)-isomer was marginally more potent than the (+)-isomer. Both isomers were equally effective at disrupting lipid bilayers.     

Open channels in sea ice (leads) as ion sources

Open channels in sea ice may be acting as sources of atmospheric ions.     

HCN2 ion channels play a central role in inflammatory and neuropathic pain

The rate of action potential firing in nociceptors is a major determinant of the intensity of pain. Possible modulators of action potential firing include the HCN ion channels, which generate an inward current, I(h), after hyperpolarization of the membrane. We found that genetic deletion of HCN2 removed the cyclic adenosine monophosphate (cAMP)-sensitive component of I(h) and abolished action potential firing caused by an elevation of cAMP in nociceptors. Mice in which HCN2 was specifically deleted in nociceptors expressing Na(V)1.8 had normal pain thresholds, but inflammation did not cause hyperalgesia to heat stimuli. After a nerve lesion, these mice showed no neuropathic pain in response to thermal or mechanical stimuli. Neuropathic pain is therefore initiated by HCN2-driven action potential firing in Na(V)1.8-expressing nociceptors.     

Structure and function of lipopolysaccharide binding protein

The primary structure of lipopolysaccharide binding protein (LBP), a trace plasma protein that binds to the lipid A moiety of bacterial lipopolysaccharides (LPSs), was deduced by sequencing cloned complementary DNA. LBP shares sequence identity with another LPS binding protein found in granulocytes, bactericidal/permeability-increasing protein, and with cholesterol ester transport protein of the plasma. LBP may control the response to LPS under physiologic conditions by forming high-affinity complexes with LPS that bind to monocytes and macrophages, which then secrete tumor necrosis factor. The identification of this pathway for LPS-induced monocyte stimulation may aid in the development of treatments for diseases in which Gram-negative sepsis or endotoxemia are involved.     

Calcium channels in planar lipid bilayers: insights into mechanisms of ion permeation and gating

Electrophysiological recordings were used to analyze single calcium channels in planar lipid bilayers after membranes from bovine cardiac sarcolemmal vesicles had been incorporated into the bilayer. In these cell-free conditions, channels in the bilayer showed unitary barium or calcium conductances, gating kinetics, and pharmacological responses that were similar to dihydropyridine-sensitive calcium channels in intact cells. The open channel current varied in a nonlinear manner with voltage under asymmetric (that is, physiological) ionic conditions. However, with identical solutions on both sides of the bilayer, the current-voltage relation was linear. In matched experiments, calcium channels from skeletal muscle T-tubules differed significantly from cardiac calcium channels in their conductance properties and gating kinetics.     

Structure and function of neuropeptide F in insects

Insect neuropeptides are a group of brain neuro-regulatory factors, which plays very important roles in growth and development, molting and metamorphosis, as well as mating and reproduction. The neuropeptide F(NPF), a multi-functional neuropeptide, is one of neuropeptides identified in numerous insect species, which plays important roles in feeding, metabolism, courtship, reproduction, aggression, ethanol sensitivity, locomotor circadian rhythms, learning and stress responses. These roles of NPF are implemented through NPF receptors(NPFR). The NPFR1, a G protein-coupled receptor with 7 transmembrane domains, is one of these receptors and is found to be important for NPF regulation. The NPF usually is consisted of around 36–40 amino acid residues, but the short neuropeptide F(sNPF) consisted of 7–16 amino acid residues have also been found in some insects. In this review, the structure and function of both NPF and sNPF in insects are discussed.