Insertion Of Channels Research Articles

Towards real-time, tracker-less 3D ultrasound guidance for spine anaesthesia.

Epidural needle insertions and facet joint injections play an important role in spine anaesthesia. The main challenge of safe needle insertion is the deep location of the target, resulting in a narrow and small insertion channel close to sensitive anatomy. Recent approaches utilizing ultrasound (US) as a low-cost and widely available guiding modality are promising but have yet to become routinely used in clinical practice due to the difficulty in interpreting US images, their limited view of the internal anatomy of the spine, and/or inclusion of cost-intensive tracking hardware which impacts the clinical workflow. We propose a novel guidance system for spine anaesthesia. An efficient implementation allows us to continuously align and overlay a statistical model of the lumbar spine on the live 3D US stream without making use of additional tracking hardware. The system is evaluated in vivo on 12 volunteers. The in vivo study showed that the anatomical features of the epidural space and the facet joints could be continuously located, at a volume rate of 0.5 Hz, within an accuracy of 3 and 7 mm, respectively. A novel guidance system for spine anaesthesia has been presented which augments a live 3D US stream with detailed anatomical information of the spine. Results from an in vivo study indicate that the proposed system has potential for assisting the physician in quickly finding the target structure and planning a safe insertion trajectory in the spine.

HCN channels enhance spike phase coherence and regulate the phase of spikes and LFPs in the theta-frequency range

What are the implications for the existence of subthreshold ion channels, their localization profiles, and plasticity on local field potentials (LFPs)? Here, we assessed the role of hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels in altering hippocampal theta-frequency LFPs and the associated spike phase. We presented spatiotemporally randomized, balanced theta-modulated excitatory and inhibitory inputs to somatically aligned, morphologically realistic pyramidal neuron models spread across a cylindrical neuropil. We computed LFPs from seven electrode sites and found that the insertion of an experimentally constrained HCN-conductance gradient into these neurons introduced a location-dependent lead in the LFP phase without significantly altering its amplitude. Further, neurons fired action potentials at a specific theta phase of the LFP, and the insertion of HCN channels introduced large lags in this spike phase and a striking enhancement in neuronal spike-phase coherence. Importantly, graded changes in either HCN conductance or its half-maximal activation voltage resulted in graded changes in LFP and spike phases. Our conclusions on the impact of HCN channels on LFPs and spike phase were invariant to changes in neuropil size, to morphological heterogeneity, to excitatory or inhibitory synaptic scaling, and to shifts in the onset phase of inhibitory inputs. Finally, we selectively abolished the inductive lead in the impedance phase introduced by HCN channels without altering neuronal excitability and found that this inductive phase lead contributed significantly to changes in LFP and spike phase. Our results uncover specific roles for HCN channels and their plasticity in phase-coding schemas and in the formation and dynamic reconfiguration of neuronal cell assemblies.

Instrument with multiple sensing channels for automated ventilation tube insertion on tympanic membrane

Otitis media with effusion (OME) is a common ear disease occurring in adults and children when the middle ear is infected, resulting in accumulation of fluid in the middle ear space and leading to complications. The current treatment is to surgically insert a ventilation tube into the tympanic membrane (TM) to bypass the Eustachian tube in draining fluid. An office-based robotic instrument allowing fast tube insertion has been designed in an earlier work of the authors. However, as the malleus bone is attached to the inner surface of the TM, this part of the membrane is to be avoided during the insertion process and the previous instrument relies on manual manipulation to locate the suitable insertion spot. In this paper, an instrument equipped with multiple sensing channels is developed to accomplish the procedure automatically. Leveraging on the machine vision and tactile sensing, the new instrument is able to manipulate the insertion channel to move effectively in the ear canal, without hitting the malleus bone to the desirable insertion spot accurately. A switching control mechanism is proposed to integrate the sensing channels and working stage. Pre-clinical tests on the harvested pig ears are carried out to verify the feasibility and efficacy of the proposed approach.

PKC enhances the capacity for secretion by rapidly recruiting covert voltage-gated Ca2+ channels to the membrane.

It is unknown whether neurons can dynamically control the capacity for secretion by promptly changing the number of plasma membrane voltage-gated Ca(2+) channels. To address this, we studied peptide release from the bag cell neurons of Aplysia californica, which initiate reproduction by secreting hormone during an afterdischarge. This burst engages protein kinase C (PKC) to trigger the insertion of a covert Ca(2+) channel, Apl Cav2, alongside a basal channel, Apl Cav1. The significance of Apl Cav2 recruitment to secretion remains undetermined; therefore, we used capacitance tracking to assay secretion, along with Ca(2+) imaging and Ca(2+) current measurements, from cultured bag cell neurons under whole-cell voltage-clamp. Activating PKC with the phorbol ester, PMA, enhanced Ca(2+) entry, and potentiated stimulus-evoked secretion. This relied on channel insertion, as it was occluded by preventing Apl Cav2 engagement with prior whole-cell dialysis or the cytoskeletal toxin, latrunculin B. Channel insertion reduced the stimulus duration and/or frequency required to initiate secretion and strengthened excitation-secretion coupling, indicating that Apl Cav2 accesses peptide release more readily than Apl Cav1. The coupling of Apl Cav2 to secretion also changed with behavioral state, as Apl Cav2 failed to evoke secretion in silent neurons from reproductively inactive animals. Finally, PKC also acted secondarily to enhance prolonged exocytosis triggered by mitochondrial Ca(2+) release. Collectively, our results suggest that bag cell neurons dynamically elevate Ca(2+) channel abundance in the membrane to ensure adequate secretion during the afterdischarge.

SPAK and OSR1 Sensitive Kir2.1 K+ Channels

Background/Aims: Kir2.1 (KCNJ2) channels are expressed in neurons, skeletal muscle and cardiac tissue and maintain the resting membrane potential. The activity of those channels is regulated by diverse signalling molecules. The present study explored whether Kir2.1 channels are sensitive to the transporter and channels regulating kinases SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are in turn regulated by WNK (with-no-K[Lys]) kinases. Methods: cRNA encoding Kir2.1 was injected into Xenopus laevis oocytes with or without additional injection of cRNA encoding wild-type SPAK, constitutively active ^T233ESPAK, WNK insensitive ^T233ASPAK, catalytically inactive ^D212ASPAK, wild-type OSR1, constitutively active ^T185EOSR1, WNK insensitive ^T185AOSR1 and catalytically inactive ^D164AOSR1. Inwardly rectifying K⁺ channel activity was quantified utilizing dual electrode voltage clamp and Kir2.1 channel protein abundance in the cell membrane was measured utilizing chemiluminescence of Kir2.1 containing an extracellular HA-tag epitope. Results: Kir2.1 activity was significantly enhanced by wild-type SPAK and ^T233ESPAK, but not by ^T233ASPAK and ^D212ASPAK, as well as by wild-type OSR1 and ^T185EOSR1, but not by ^T185AOSR1 and ^D164AOSR1. As shown for SPAK, the kinases enhanced Kir2.1 protein abundance in the cell membrane. The difference of current and conductance between oocytes expressing Kir2.1 together with SPAK or OSR1 and oocytes expressing Kir2.1 alone was dissipated following a 24 hours inhibition of channel insertion into the cell membrane by brefeldin A (5 µM). Conclusions: SPAK and OSR1 are both stimulators of Kir2.1 activity. They are presumably effective by enhancing channel insertion into the cell membrane.

Biological Channel Confinement in Nanostructured Nanopore

The main challenge in the area of artificial single nanopores prepared by track-etched polymer sheets or transmission electron microscopy irradiation of thin silicon nitride film consists of mimicking biological channels.[1]1 In this context, the recent demonstration of the feasibility of hybrid biological/artificial solid-state nanopores by direct insertion of biological channels is likely the most original and promising way.[2]2 This strategy aims to combine the advantages of both solid-state nanopores (robustness, number, size and shape control) and biological channels (selectivity, precise structure). [3]3Here we will discuss about biological channel confinement inside single pore PET track-etched nanopore.Firstly, we will show that how the diameter pore size affects the ionic transport of gramicidin A (gA). Indeed when the gA is confined inside nanopores (10.6 nm, 5.7 nm, ∼2 nm), its exhibits an anionic behavior explained by the loss of gA head-head dimer structure. The conductance measurements reveal for the first time an enhanced ionic transport mechanism through gA inside a polymeric solid state nanopore as in biological membranes.

Ionic selectivity of nystatin A1 confined in nanoporous track-etched polymer membrane.

The hybrid biological/polymeric solid-state nanopore membrane offers several opportunities to combine the advantage of biological channel (selectivity) and material (robustness). Based on this technology, the challenge is to obtain selective ionic exchange membranes, with no energy intake. The direct insertion of an ionic channel inside a nanopore should be a promise solution. Here, the authors report a hybrid nanopore based on nystatin A1 confinement in commercial nanopore membrane. Ionic transport and selectivity studies show that the hybrid nanopores exhibit mainly an anionic behaviour, on the contrary to biological conditions. However, the order of magnitude between the different ratios of permeation of several cationic species is retained even if the blocking of divalent cation is not totally proved.

Trafficking of ThermoTRP Channels.

ThermoTRP channels (thermoTRPs) define a subfamily of the transient receptor potential (TRP) channels that are activated by changes in the environmental temperature, from noxious cold to injurious heat. Acting as integrators of several stimuli and signalling pathways, dysfunction of these channels contributes to several pathological states. The surface expression of thermoTRPs is controlled by both, the constitutive and regulated vesicular trafficking. Modulation of receptor surface density during pathological processes is nowadays considered as an interesting therapeutic approach for management of diseases, such as chronic pain, in which an increased trafficking is associated with the pathological state. This review will focus on the recent advances trafficking of the thermoTRP channels, TRPV1, TRPV2, TRPV4, TRPM3, TRPM8 and TRPA1, into/from the plasma membrane. Particularly, regulated membrane insertion of thermoTRPs channels contributes to a fine tuning of final channel activity, and indeed, it has resulted in the development of novel therapeutic approaches with successful clinical results such as disruption of SNARE-dependent exocytosis by botulinum toxin or botulinomimetic peptides.

Functional surface engineering by nucleotide-modulated potassium channel insertion into polymer membranes attached to solid supports

Planar solid-supported membranes based on amphiphilic block copolymers represent promising systems for the artificial creation of structural surfaces. Here we introduce a method for engineering functional planar solid-supported membranes through insertion of active biomolecules. We show that membranes based on poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) (PDMS-b-PMOXA) amphiphilic diblock copolymers, which mimic natural membranes, are suitable for hosting biomolecules. Our strategy allows preparation of large-area, well-ordered polymer bilayers via Langmuir–Blodgett and Langmuir–Schaefer transfers, and insertion of biomolecules by using Bio-Beads. We demonstrate that a model membrane protein, the potassium channel from the bacterium Mesorhizobium loti, remains functional after insertion into the planar solid-supported polymer membrane. This approach can be easily extended to generate a platform of functional solid-supported membranes by insertion of different hydrophobic biomolecules, and employing different types of solid substrates for desired applications.

An Enhanced Color Shift Keying Modulation Scheme for High-Speed Wireless Visible Light Communications

This paper presents a new color shift keying (CSK) modulation format for wireless visible light communication (VLC), based on four colors instead of the three colors used in the existing IEEE 802.15.7 CSK physical layer standard. The new four color system uses a novel intensity modulation and direct detection approach to realize a four-dimensional signaling scheme that uses the available color and signal spaces efficiently. The bit error rate evaluation of both the existing and proposed system shows that the new four color scheme achieves a significant 4.4-dB electrical SNR gain over the three color scheme for an additive white Gaussian noise channel. The performance of existing and proposed CSK systems is examined over a range of dispersive optical wireless channels including the channel crosstalk and insertion losses, which reveals that the four color CSK scheme is more power efficient and reliable than the three color scheme for a particular amount of delay spread that the optical wireless channel may have.

Pseudo painting/air bubble technique for planar lipid bilayers.

A functional reconstitution of channel proteins in planar lipid bilayers is still very versatile to study structure/function correlates under well-defined conditions at the single protein level. In this study we present an improved planar lipid bilayer technique in which an air bubble is used for stabilizing unstable/leaky bilayers or for removing excess lipids. The bubble can also be used as a tool for reducing the number of channels in the bilayer with the goal of having only one active channel in the membrane. Stable planar lipid bilayers are formed within seconds to minutes. In the case of multiple channel insertion the air bubble can be used to reduce the number of channels within minutes. The simple improvement of the classical folding technique guarantees a very fast creation of stable bilayers even with difficult phospholipids in a conventional vertical bilayer set-up; it requires no modifications of the existing set-up. This technique is very easy to handle and guarantees successful single channel recordings for any kind of planar lipid bilayer experiment.

Upregulation of the large conductance voltage- and Ca2+-activated K+ channels by Janus kinase 2

The iberiotoxin-sensitive large conductance voltage- and Ca(2+)-activated potassium (BK) channels (maxi-K(+)-channels) hyperpolarize the cell membrane thus supporting Ca(2+) entry through Ca(2+)-release activated Ca(2+) channels. Janus kinase-2 (JAK2) has been identified as novel regulator of ion transport. To explore whether JAK2 participates in the regulation of BK channels, cRNA encoding Ca(2+)-insensitive BK channels (BK(M513I+Δ899-903)) was injected into Xenopus oocytes with or without cRNA encoding wild-type JAK2, gain-of-function (V617F)JAK2, or inactive (K882E)JAK2. K(+) conductance was determined by dual electrode voltage clamp and BK-channel protein abundance by confocal microscopy. In A204 alveolar rhabdomyosarcoma cells, iberiotoxin-sensitive K(+) current was determined utilizing whole cell patch clamp. A204 cells were further transfected with JAK2 and BK-channel transcript, and protein abundance was quantified by RT-PCR and Western blotting, respectively. As a result, the K(+) current in BK(M513I+Δ899-903)-expressing oocytes was significantly increased following coexpression of JAK2 or (V617F)JAK2 but not (K882E)JAK2. Coexpression of the BK channel with (V617F)JAK2 but not (K882E)JAK2 enhanced BK-channel protein abundance in the oocyte cell membrane. Exposure of BK-channel and (V617F)JAK2-expressing oocytes to the JAK2 inhibitor AG490 (40 μM) significantly decreased K(+) current. Inhibition of channel insertion by brefeldin A (5 μM) decreased the K(+) current to a similar extent in oocytes expressing the BK channel alone and in oocytes expressing the BK channel and (V617F)JAK2. The iberiotoxin (50 nM)-sensitive K(+) current in rhabdomyosarcoma cells was significantly decreased by AG490 pretreatment (40 μM, 12 h). Moreover, overexpression of JAK2 in A204 cells significantly enhanced BK channel mRNA and protein abundance. In conclusion, JAK2 upregulates BK channels by increasing channel protein abundance in the cell membrane.

The Perforin Pore Facilitates the Delivery of Cationic Cargos

Cytotoxic lymphocytes eliminate virally infected or neoplastic cells through the action of cytotoxic proteases (granzymes). The pore-forming protein perforin is essential for delivery of granzymes into the cytoplasm of target cells; however the mechanism of this delivery is incompletely understood. Perforin contains a membrane attack complex/perforin (MACPF) domain and oligomerizes to form an aqueous pore in the plasma membrane; therefore the simplest (and best supported) model suggests that granzymes passively diffuse through the perforin pore into the cytoplasm of the target cell. Here we demonstrate that perforin preferentially delivers cationic molecules while anionic and neutral cargoes are delivered inefficiently. Furthermore, another distantly related pore-forming MACPF protein, pleurotolysin (from the oyster mushroom), also favors the delivery of cationic molecules, and efficiently delivers human granzyme B. We propose that this facilitated diffusion is due to conserved features of oligomerized MACPF proteins, which may include an anionic lumen.

Intramolecular Disulfide Bond of Tim22 Protein Maintains Integrity of the TIM22 Complex in the Mitochondrial Inner Membrane

Mitochondrial proteins require protein machineries called translocators in the outer and inner membranes for import into and sorting to their destination submitochondrial compartments. Among them, the TIM22 complex mediates insertion of polytopic membrane proteins into the inner membrane, and Tim22 constitutes its central insertion channel. Here we report that the conserved Cys residues of Tim22 form an intramolecular disulfide bond. By comparison of Tim22 Cys → Ser mutants with wild-type Tim22, we show that the disulfide bond of Tim22 stabilizes Tim22 especially at elevated temperature through interactions with Tim18, which are also important for the stability of the TIM22 complex. We also show that lack of the disulfide bond in Tim22 impairs the assembly of TIM22 pathway substrate proteins into the inner membrane especially when the TIM22 complex handles excess amounts of substrate proteins. Our findings provide a new insight into the mechanism of the maintenance of the structural and functional integrity of the TIM22 complex.

Lithium Causes G2 Arrest of Renal Principal Cells

Vasopressin-regulated expression and insertion of aquaporin-2 channels in the luminal membrane of renal principal cells is essential for urine concentration. Lithium affects urine concentrating ability, and approximately 20% of patients treated with lithium develop nephrogenic diabetes insipidus (NDI), a disorder characterized by polyuria and polydipsia. Lithium-induced NDI is caused by aquaporin-2 downregulation and a reduced ratio of principal/intercalated cells, yet lithium induces principal cell proliferation. Here, we studied how lithium-induced principal cell proliferation can lead to a reduced ratio of principal/intercalated cells using two-dimensional and three-dimensional polarized cultures of mouse renal collecting duct cells and mice treated with clinically relevant lithium concentrations. DNA image cytometry and immunoblotting revealed that lithium initiated proliferation of mouse renal collecting duct cells but also increased the G2/S ratio, indicating G2/M phase arrest. In mice, treatment with lithium for 4, 7, 10, or 13 days led to features of NDI and an increase in the number of principal cells expressing PCNA in the papilla. Remarkably, 30%-40% of the PCNA-positive principal cells also expressed pHistone-H3, a late G2/M phase marker detected in approximately 20% of cells during undisturbed proliferation. Our data reveal that lithium treatment initiates proliferation of renal principal cells but that a significant percentage of these cells are arrested in the late G2 phase, which explains the reduced principal/intercalated cell ratio and may identify the molecular pathway underlying the development of lithium-induced renal fibrosis.

Up-Regulation of Kir2.1 (KCNJ2) by the Serum & Glucocorticoid Inducible SGK3

Background/Aims: The serum & glucocorticoid inducible kinase SGK3, an ubiquitously expressed serine/threonine kinase, regulates a variety of ion channels. It has previously been shown that SGK3 upregulates the outwardly rectifying K⁺ channel K_V11.1, which is expressed in cardiomyocytes. Cardiomyocytes further express the inward rectifier K⁺ channel K_ir2.1, which contributes to maintenance of resting cell membrane potential. Loss-of-function mutations of KCNJ2 encoding K_ir2.1 result in Andersen-Tawil syndrome with periodic paralysis, cardiac arrhythmia and dysmorphic features. The present study explored whether SGK3 participates in the regulation of K_ir2.1. Methods: cRNA encoding K_ir2.1 was injected into Xenopus oocytes with and without additional injection of cRNA encoding wild type SGK3, constitutively active ^S419DSGK3 or inactive ^K191NSGK3. K_ir2.1 activity was determined by two-electrode voltage-clamp and K_ir2.1 protein abundance in the cell membrane by immunostaining and subsequent confocal imaging or by chemiluminescence. Results: Injection of 10 ng cRNA encoding wild type SGK3 and ^S419DSGK3, but not ^K191NSGK3 significantly enhanced K_ir2.1-mediated currents. SGK inhibitor EMD638683 (50 µM) abrogated ^S419DSGK3-induced up-regulation of K_ir2.1. Moreover, wild type SGK3 enhanced the channel protein abundance in the cell membrane. The decay of K_ir2.1-mediated currents following inhibition of channel insertion into the cell membrane by brefeldin A (5 µM) was similar in oocytes coexpressing K_ir2.1 and SGK3 as in oocytes expressing K_ir2.1 alone, suggesting that SGK3 influences channel insertion into rather than channel retrieval from the cell membrane. Conclusions: SGK3 is a novel regulator of K_ir2.1.

Computational Characterization of the Disordered Ensembles of Vasopressin and Oxytocin

Vasopressin and oxytocin are intrinsically disordered cyclic nanopeptides belonging to a family of neurohypophysial hormones. Vasopressin is an antidiuretic, regulating the retention of water and salts in mammals by indirectly promoting the insertion of aquaporin-2 channels into the epithelial cells of kidney nephron collecting ducts. Oxytocin, in contrast, is a neurotransmitter responsible for inducing labor and the subsequent lactation, as well as modulating some social behaviors. Although unique in their functions, these peptides only differ by two residues and both feature a tocin ring formed by the disulfide bridge between 1st and 6th cysteine residues. This structural similarity was experimentally linked to inhibition of activity at vasopressin receptors by the present oxytocin. Conversely, previous studies have also shown that single-residue mutations in both peptides have a significant impact on their receptor specificities.In this study we perform molecular dynamics (MD) simulations of wild type and mutant oxytocin and vasopressin in order to characterize their structural ensembles and relate them to the observed variation in activity. The generated ensembles of Y21H and P26L mutants of vasopressin and Q23T and Q23T,P26G mutants of oxytocin reveal significant population shifts compared to the wild type peptides. Here we present the classification of these populations based on the distribution of radius of gyration and deformation of the tocin ring, and attempt to relate the structural changes to the experimentally determined peptide activity and carrier protein binding affinity.

Focal damage to macaque photoreceptors produces persistent visual loss

Insertion of light-gated channels into inner retina neurons restores neural light responses, light evoked potentials, visual optomotor responses and visually-guided maze behavior in mice blinded by retinal degeneration. This method of vision restoration bypasses damaged outer retina, providing stimulation directly to retinal ganglion cells in inner retina. The approach is similar to that of electronic visual protheses, but may offer some advantages, such as avoidance of complex surgery and direct targeting of many thousands of neurons. However, the promise of this technique for restoring human vision remains uncertain because rodent animal models, in which it has been largely developed, are not ideal for evaluating visual perception. On the other hand, psychophysical vision studies in macaque can be used to evaluate different approaches to vision restoration in humans. Furthermore, it has not been possible to test vision restoration in macaques, the optimal model for human-like vision, because there has been no macaque model of outer retina degeneration. In this study, we describe development of a macaque model of photoreceptor degeneration that can in future studies be used to test restoration of perception by visual prostheses. Our results show that perceptual deficits caused by focal light damage are restricted to locations at which photoreceptors are damaged, that optical coherence tomography (OCT) can be used to track such lesions, and that adaptive optics retinal imaging, which we recently used for in vivo recording of ganglion cell function, can be used in future studies to examine these lesions.

Shear stress triggers insertion of voltage-gated potassium channels from intracellular compartments in atrial myocytes

Atrial myocytes are continuously exposed to mechanical forces including shear stress. However, in atrial myocytes, the effects of shear stress are poorly understood, particularly with respect to its effect on ion channel function. Here, we report that shear stress activated a large outward current from rat atrial myocytes, with a parallel decrease in action potential duration. The main ion channel underlying the increase in current was found to be Kv1.5, the recruitment of which could be directly observed by total internal reflection fluorescence microscopy, in response to shear stress. The effect was primarily attributable to recruitment of intracellular pools of Kv1.5 to the sarcolemma, as the response was prevented by the SNARE protein inhibitor N-ethylmaleimide and the calcium chelator BAPTA. The process required integrin signaling through focal adhesion kinase and relied on an intact microtubule system. Furthermore, in a rat model of chronic hemodynamic overload, myocytes showed an increase in basal current despite a decrease in Kv1.5 protein expression, with a reduced response to shear stress. Additionally, integrin beta1d expression and focal adhesion kinase activation were increased in this model. This data suggests that, under conditions of chronically increased mechanical stress, the integrin signaling pathway is overactivated, leading to increased functional Kv1.5 at the membrane and reducing the capacity of cells to further respond to mechanical challenge. Thus, pools of Kv1.5 may comprise an inducible reservoir that can facilitate the repolarization of the atrium under conditions of excessive mechanical stress.

Bounds on the Capacity of Random Insertion and Deletion-Additive Noise Channels

We develop several analytical lower bounds on the capacity of binary insertion and deletion channels by considering independent uniformly distributed (i.u.d.) inputs and computing lower bounds on the mutual information between the input and output sequences. For the deletion channel, we consider two different models: i.i.d. deletion–substitution channel and i.i.d. deletion channel with additive white Gaussian noise (AWGN). These two models are considered to incorporate effects of the channel noise along with the synchronization errors. For the insertion channel case, we consider Gallager's model in which the transmitted bits are replaced with two random bits and uniform over the four possibilities independently of any other insertion events. The general approach taken is similar in all cases, however the specific computations differ. Furthermore, the approach yields a useful lower bound on the capacity for a wide range of deletion probabilities of the deletion channels, while it provides a beneficial bound only for small insertion probabilities (less than 0.25) of the insertion model adopted. We emphasize the importance of these results by noting that: 1) our results are the first analytical bounds on the capacity of deletion-AWGN channels, 2) the results developed are the best available analytical lower bounds on the deletion–substitution case, 3) for the Gallager insertion channel model, the new lower bound improves the existing results for small insertion probabilities.