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New catalysts have been developed and studied for the synthesis of acetaldehyde and acetone in combination with acetylene hydration. The composition of the feedstock CCP catalyst used in the acetaldehyde synthesis was analyzed and identified. Based on the analysis results, active cadmium oxide was separated from the CCP catalyst composition, and new BCC-1, BCC-2, BCC-3, BCC-4, BCC-5, BCC-6, BCC-7, BCC-8, BCC-9 catalysts were prepared. These catalysts were tested, and during the acetaldehyde synthesis process, the BCC-7 catalyst yielded a high efficiency (65.7%). Optimal conditions were determined for the synthesis of acetaldehyde and acetone. Bentonite mineral was used as a core in the preparation of this catalyst. There are different brands of bentonite mineral, and Bentonite (PBG) brand mineral was used for BCC-7 catalyst. The high content of aluminum oxide in this mineral increases the strength of the catalyst.

The article presents the results of the yield of pyridine derivatives obtained on the basis of a catalyst of various compositions and, at the same time, the efficiency of new catalytic systems for the synthesis of pyridine derivatives is investigated. “Angren kaolin” (Uzbekistan) was used to develop catalytic systems. The development and implementation of new catalytic systems leads to a decrease in the problems associated with the purchase of catalysts from abroad and will entail economic benefits for the republic. To solve the problems, the following research methods were used: spectral analysis, microscopic analysis, potentiometric method, physicochemical methods of analysis, and methods of preparing catalysts.The catalysts have been developed with different ratios of starting components. The efficiency of heterogeneous catalysts was determined by the synthesis of pyridine derivatives at the facilities of JSC “Navoiyazot”. It was found that among the monocomponent catalysts, the CK-13 brand catalyst ((CdO-13.0%, kaolin-87.0%) (2-methylpyridine-41.2%, 4- methylpyridine-22.4%) was more efficient) with a yield of 63.6%, and among two-component catalysts of the CChK-13 brand (CdO-13.0%, Cr2O3-5.0%, kaolin-82.0%) (2-methylpyridine-45.4%, 4-methylpyridine - 24.8%)) with a yield of 70.2%. And also the influence of peptizers on the yield of finished products was studied.

The article shows the importance of obtaining new composition of heavy drilling fluids based on composite chemical reagents from local raw materials and industrial wastes for drilling oil and gas wells. In the process of building oil and gas wells to maintain the stability of the walls, to prevent the flow of salts, and to prevent the penetration of formation fluids into the well, it becomes necessary to increase the density of the drilling fluid, which can be accomplished by introducing components with increased density. For obtaining and stabilization heavy drilling fluid were investigated and recommended new compositions of powder water soluble gossypol resin and carboxymetylcellylose sodium and other minerals. Stabilization indexes and their determination in the drilling process of oil and gas wells have been investigated. The result of research have been implemented in the drilling process of oil and gas wells with abnormally high reservoir pressure.

The convergence of conditioned and unconditioned stimuli (CS and US) into the lateral amygdala (LA) serves as a substrate for an adequate fear response in vivo. This well-known Pavlovian paradigm modulates the synaptic plasticity of neurons, as can be proved by the long-term potentiation (LTP) phenomenon in vitro. Although there is an increasing body of evidence for the existence of LTP in the amygdala, only a few studies were able to show a reliable long-term depression (LTD) of excitation in this structure. We have used coronal brain slices and conducted patch-clamp recordings in pyramidal neurons of the lateral amygdala (LA). After obtaining a stable baseline excitatory postsynaptic current (EPSC) response at a holding potential of -70 mV, we employed a paired-pulse paradigm at 1 Hz at the same membrane potential and could observe a reliable LTD. The different durations of stimulation (ranging between 1.5-24 min) were tested first in the same neuron, but the intensity was kept constant. The latter paradigm resulted in a step-wise LTD with a gradually increasing magnitude under these conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). All rights reserved.)

Mollusks, including snails, possess two chambered hearts. The heart and cardiomyocytes of snails have many similarities with those of mammals. Also, the biophysics and pharmacology of Ca, K, and Na ion channels resemble. Similar to mammals, in mollusks, the ventricular cardiomyocytes and K channels are often studied, which are selectively sensitive to antagonists such as 4-AP, E-4031, and TEA. Since the physiological properties of the ventricular cardiac cells of snails are well characterized, the enzymatically dissociated atrial cardiomyocytes of Cornu aspersum (Müller, 1774) were studied using the whole-cell patch-clamp technique for detailed comparisons with mice, Mus musculus. The incubation of tissues in a solution simultaneously containing two enzymes, collagenase and papain, enabled the isolation of single cells. Recordings in the atrial cardiomyocytes of snails revealed outward K + currents closely resembling those of the ventricle. The latter was consistent, whether the voltage ramp or steps and long or short pulses were used. Interestingly, under identical conditions, the current waveforms of atrial cardiomyocytes in snails were similar to those of mice left ventricles, albeit the kinetics and the absence of inward rectifier K channel (I K1 ) activation. Therefore, the heart of mollusks could be used as a simple and accessible experimental model, particularly for pharmacology and toxicology studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Voltage-dependent K + (Kv) channels are diverse, comprising the classical Shab  - Kv2, Shaker  - Kv1, Shal  - Kv4, and Shaw  - Kv3 families. The Shaker family alone consists of Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5, Kv1.6, and Kv1.7. Moreover, the Shab family comprises two functional (Kv2.1 and Kv2.2) and several "silent" alpha subunits (Kv2.3, Kv5, Kv6, Kv8, and Kv9), which do not generate K current. However, e.g., Kv8.1, via heteromerization, inhibits outward currents of the same family or even that of Shaw . This property of Kv8.1 is similar to those of designated beta subunits or non-selective auxiliary elements, including ADAM or AMIGO proteins. Kv channels and, in turn, ADAM may modulate the synaptic long-term potentiation (LTP). Prevailingly, Kv1.1 and Kv1.5 are attributed to respective brain and heart pathologies, some of which may occur simultaneously. The aforementioned channel proteins are apparently involved in several brain pathologies, including schizophrenia and seizures., Competing Interests: Conflict of interestThe author declares no competing interests., (© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The patch-clamp technique represents an electrophysiology type of method. This is one of several insightful approaches with five major configurations, namely a loose patch, cell-attached (also known as on-cell), whole-cell, inside-out, and outside-out modes. The patch-clamp method is more advanced compared to classical electrophysiology since it elucidates single-channel activation in a tiny portion of the membrane in addition to action potential (AP), junction potential (JP), endplate potential (EP), electrical coupling between two adjacent cells via Gap junction hemi-channels, excitatory/inhibitory postsynaptic potentials, and resting membrane potential (RMP). In fact, a malfunction of only one channel or even one component will alter AP amplitude or duration in vitro. If parameters are inferred appropriately and recordings are performed properly, the patch-clamp trace readouts and results are robust. The main hallmarks of currents via voltage-dependent calcium (Cav), hyperpolarization-activated cyclic nucleotide gated non-selective cation (HCN), inwardly rectifying potassium (Kir), voltage-dependent potassium (Kv), and voltage-dependent sodium (Nav) channels are similar and tractable among cells even when they are derived from evolutionary distinct organs and species. However, the size of the membrane area, where the functional subunits reside, and current magnitudes vary among cells of the same type. Therefore, dividing current magnitudes by cell capacitance- current density enables the estimate of functional and active channels relative to recorded cytoplasmic membrane area. Since the patch-clamp recordings can be performed in both current- and voltage-clamp modes, the action potential or spike durations can be adequately elucidated. Sometimes, optical methods are preferred to patch-clamp electrophysiology, but the obtained signals and traces are not robust. Finally, not only an alternans of AP durations, but also that of 'action potential shape' is observed with electrophysiology., Competing Interests: Conflict of interestThe author declares no conflict of interest., (© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2023.)

The functioning of voltage-dependent K channels (Kv) may correlate with the physiological state of brain in organisms, including the sleep in Drosophila. Apparently, all major types of K currents are expressed in CNS of this model organism. These are the Shab-Kv2, Shaker-Kv1, Shal-Kv4, and Shaw-Kv3 α subunits and can be deciphered by patch-clamp technique. Although it is plausible that some of these channels may play a prevailing role in sleep or wakefulness, several of recent data are not conclusive. It needs to be defined that indeed the frequency of action potentials in large ventral lateral pacemaker neurons is either higher or lower during the morning or night because of an increased Kv3 and Kv4 currents, respectively. The outcomes of dynamic-clamp approach in combination with electrophysiology in insects are unreliable in contrast to those in mammalian neurons. Since the addition of virtual Kv conductance during any Zeitgeber time should not significantly alter the resting membrane potential. This review explains the Drosophila sleep behavior based on neural activity with respect to K current-driven action potential rate., (© 2022 Wiley Periodicals LLC.)

Whether or not the hyperpolarization-activated cyclic nucleotide-gated nonselective cation channel (HCN or funny current I f ) is involved in pacemaking - recurrent heartbeat, it is attributed to electrical activities in all excitable cells, including those of invertebrates. In latter group of animals prevailingly the electrical signals and function of heart in terms of chrono- and inotropy are elucidated. Although in simpler models including insects experimental outcomes are reproducible and robust, involvement of "cardiac clock" mechanism in pacemaking is not conclusive. In this assay, the mechanisms of heartbeat are synthesized by focused comparisons between insect and mammalian hearts., (© 2022 Wiley Periodicals LLC.)

We have experimented with isolated cardiomyocytes of mollusks Helix. During the whole-cell patch-clamp recordings of K + currents a considerable decrease in amplitude was observed upon repeated voltage steps at 0.96 Hz. For these experiments, ventricular cells were depolarized to identical + 20 mV from a holding potential of - 50 mV. The observed spontaneous inhibition of outward currents persisted in the presence of 4-aminopyridine, tetraethylammonium chloride or E-4031, the selective class III antiarrhythmic agent that blocks HERG channels. Similar tendency was retained when components of currents sensitive to either 4-AP or TEA were mathematically subtracted. Waveforms of currents sensitive to 1 and 10 micromolar concentration of E-4031 were distinct comprising prevailingly those activated during up to 200 ms pulses. The outward current activated by a voltage ramp at 60 mV x s -1 rate revealed an inward rectification around + 20 mV. This feature closely resembles those of the mammalian cardiac delayed rectifier I Kr ., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The depolarization is also important for the short-term synaptic plasticity, known as depolarization-induced suppression of excitation (DSE). The two major types of neurons and their synapses in the lateral nucleus of amygdala (LA) are prone to plasticity. However, DSE in interneurons has not been reported in amygdala in general and in LA in particular. Therefore, we conducted the patch-clamp experiments with LA interneurons. These neurons were identified by lack of adaptation in firing rate of action potentials. In this study, we show for the first time a transient suppression of neurotransmission at synapses both within the local network and between cortical inputs and interneurons of the LA. The retrograde neurotransmission from GABAergic interneurons were comparable with that of glutamatergic pyramidal cells. That is the axonal terminals of cortical inputs do not posses selectivity toward two neuronal subtypes. However, the DSE of both types of neurons involve an increase in intracellular Ca 2+ and the release of endogenous cannabinoids (eCB) and activation of presynaptic CB1 receptors. The magnitude of DSE was significantly higher in interneurons compared with pyramidal cells, though developed with some latency., (© 2021 Kodirov et al.; Published by Cold Spring Harbor Laboratory Press.)

The largest biomass of channel proteins is located in unicellular organisms and bacteria that have no organs. However, orchestrated bidirectional ionic currents across the cell membrane via the channels are important for the functioning of organs of organisms, and equally concern both fauna or flora. Several ion channels are activated in the course of action potentials. One of the hallmarks of voltage-dependent channels is a 'tail current' - deactivation as observed after prior and sufficient activation predominantly at more depolarized potentials e.g. for Kv while upon hyperpolarization for HCN α subunits. Tail current also reflects the timing of channel closure that is initiated upon termination of stimuli. Finally, deactivation of currents during repolarization could be a selective estimate for given channel as in case of HERG, if dedicated long and more depolarized 'tail pulse' is used. Since from a holding potential of e.g. -70 mV are often a family of outward K + currents comprising I A and I K are simultaneously activated in native cells., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Effects of ibutilide, a class III antiarrhythmic drug, on delayed rectifier potassium currents (I K ) in freshly isolated guinea pig ventricular myocytes were studied. Experiments were performed using the whole-cell configuration of patch-clamp technique under blockade of L-type calcium currents (Cav1). Ibutilide at concentrations ranging between 10 nM and 100 µM inhibited I Kr in dose-dependent manner with a half maximal effective concentration of 2.03 ± 0.74 µM (n = 5-10). The amplitude of tail currents activated by prepulse to + 20 mV was decreased from 253 ± 52 to 130 ± 25 pA (n = 8, p < 0.01) in the presence of 1 µM ibutilide. The envelope test revealed time-dependent changes in ratio of I K-tail /ΔI K during 0.2-2 s pulse durations in the absence of drug. With ibutilide, regardless of pulse duration, a relatively constant ratio was estimated, indicative of predominant involvement of I Kr component. The slow I Ks persisted to greater extent even at 100 μM ibutilide revealing a distinguishable selectivity toward the I Kr component.

Great interest in the comparative physiology of hearts and their functions in Animalia has emerged with classic papers on Limulus polyphemus and mollusks. The recurrent cardiac activity-heart rate-is the most important physiological parameter and when present the kardia (Greek) is vital to the development of entire organs of the organisms in the animal kingdom. Extensive studies devoted to the regulation of cardiac rhythm in invertebrates have revealed that the basics of heart physiology are comparable to mammals. The hearts of invertebrates also beat spontaneously and are supplied with regulatory nerves: either excitatory or inhibitory or both. The distinct nerves and the source of excitation/inhibition at the level of single neurons are described for many invertebrate genera. The vertebrates and a majority of invertebrates have myogenic hearts, whereas the horseshoe crab L. polyphemus and a few other animals have a neurogenic cardiac rhythm. Nevertheless, the myogenic nature of heartbeat is precursor, because the contraction of native and stem-cell-derived cardiomyocytes does occur in the absence of any neural elements. Even in L. polyphemus, the heart rhythm is myogenic at embryonic stages., (© 2018 Wiley Periodicals, Inc.)

Since the reward center is considered to be the area tegmentalis ventralis of the hypothalamus, logically its neurons could mainly be responsible for addiction. However, the literature asserts that almost any neurons of CNS can respond to one or another addictive compound. Obviously not only addictive nicotine, but also alcohol, amphetamine, cannabis, cocaine, heroin and morphine may influence dopaminergic cells alone in VTA. Moreover, paradoxically some of these drugs ameliorate symptoms, counterbalance syndromes, cure diseases and improve health, not only those related to the CNS and in adults, but also almost all other organs and in children, e.g. epilepsy., Competing Interests: Conflicting interests The author has declared that no conflict of interests exist.

The majority of neurons in lateral septum (LS) are electrically silent at resting membrane potential. Nicotine transiently excites a subset of neurons and occasionally leads to long lasting bursting activity upon longer applications. We have observed simultaneous changes in frequencies and amplitudes of spontaneous action potentials (AP) in the presence of nicotine. During the prolonged exposure, nicotine increased numbers of spikes within a burst. One of the hallmarks of nicotine effects was the occurrences of double spikes (known also as bursting). Alignment of 51 spontaneous spikes, triggered upon continuous application of nicotine, revealed that the slope of after-depolarizing potential gradually increased (1.4 vs. 3 mV/ms) and neuron fired the second AP, termed as double spiking. A transition from a single AP to double spikes increased the amplitude of after-hyperpolarizing potential. The amplitude of the second (premature) AP was smaller compared to the first one, and this correlation persisted in regard to their duration (half-width). A similar bursting activity in the presence of nicotine, to our knowledge, has not been reported previously in the septal structure in general and in LS in particular.

The effects of addictive drugs most commonly occur via interactions with target receptors. The same is true of nicotine and its multiple receptors in a variety of cell types. However, there are also side effects for given substances that can dramatically change cellular, tissue, organ, and organism functions. In this study, we present evidence that nicotine possesses such properties, and modulates neuronal excitability. We recorded whole-cell voltages and currents in neurons situated in the dorsal portion of the lateral septum in acute coronal brain slices of adult rats. Our experiments in the lateral septum revealed that nicotine directly affects HCN - hyperpolarization-activated cyclic nucleotide gated non-selective cation channels. We demonstrate that nicotine effects persist despite the concurrent application of nicotinic acetylcholine receptors' antagonists - mecamylamine, methyllycaconitine, and dihydro-β-erythroidine. These results are novel in regard to HCN channels in the septum, in general, and in their sensitivity to nicotine, in particular., (Published by Elsevier Ltd.)

In this manuscript, I review the current and relevant classical studies on properties of the Mollusca heart and their central nervous system including ganglia, neurons, and nerves involved in cardiomodulation. Similar to mammalian brain hemispheres, these invertebrates possess symmetrical pairs of ganglia albeit visceral (only one) ganglion and the parietal ganglia (the right ganglion is bigger than the left one). Furthermore, there are two major regulatory drives into the compartments (pericard, auricle, and ventricle) and cardiomyocytes of the heart. These are the excitatory and inhibitory signals that originate from a few designated neurons and their putative neurotransmitters. Many of these neurons are well-identified, their specific locations within the corresponding ganglion are mapped, and some are termed as either heart excitatory (HE) or inhibitory (HI) cells. The remaining neurons are classified as cardio-regulatory, and their direct and indirect actions on the heart's function have been documented. The cardiovascular anatomy of frequently used experimental animals, Achatina, Aplysia, Helix, and Lymnaea is relatively simple. However, as in humans, it possesses all major components including even trabeculae and atrio-ventricular valves. Since the myocardial cells are enzymatically dispersible, multiple voltage dependent cationic currents in isolated cardiomyocytes are described. The latter include at least the A-type K(+), delayed rectifier K(+), TTX-sensitive Na(+), and L-type Ca(2+) channels., (Published by Elsevier Inc.)

In this review the recent studies related to the voltage dependent K+ channels are discussed. During the last 15 years the molecular cloning revealed a large number of alpha-subunits of voltage dependent K+ channels. This approach enabled to elucidate the properties of different types of channels and, in particular, characteristics of such structural elements as auxiliary subunits. These subunits are mainly responsible for the ionic permeability features of alpha-subunits. There are several cytoplasmic and membrane-associated auxiliary subunits such as beta-subunits, minK (minimal K+ channel peptide), MiRP (minK-related peptide), KChAP (K+ channel-associated protein), KChIP (K+ channel-interacting protein) and NCS (neuronal calcium sensor).

The amygdala is a key area of the brain where the emotional memories are stored throughout the lifespan. It is well established that synapses in the lateral nucleus of amygdala (LA) can undergo long-term potentiation, a putative cellular correlate of learning and memory. However, a type of short-term synaptic plasticity, known as depolarization-induced suppression of excitation (DSE), has not been studied previously in the amygdala in general and in the LA in particular. In this study we aimed to prove either the absence or the presence of this phenomenon in the LA. Our data demonstrate for the first time that DSE is present in the LA and that it modulates the cortical excitatory synaptic input into this region. The existence of this type of retrograde neurotransmission in glutamatergic pyramidal neurons of the LA suggests that the axonal terminals of cortical inputs do possess functional type 1 cannabinoid receptors, and provides a novel insight regarding inputs into the LA. Further experiments indeed revealed endocannabinoids as the messenger for this retrograde signaling in the LA. In conclusion, the DSE may play a functional role in synaptic plasticity and related emotional memory processing in the LA.

The functional role of releasable Zn2+ in the central nervous system remains unknown. Here we show that zinc transporter 3 (ZnT-3), which maintains a high concentration of Zn2+ in synaptic vesicles and serves as a marker for zinc-containing neurons, is enriched in the lateral nucleus of the amygdala and in the temporal area 3 of the auditory cortex, an area that conveys information about the auditory conditioned stimulus to the lateral nucleus of the amygdala, but not in other conditioned stimulus areas located in the auditory thalamus. Using whole-cell recordings from amygdala slices, we demonstrated that activity-dependent release of chelatable Zn2+ is required for the induction of spike timing-dependent long-term potentiation in cortical input to the amygdala implicated in fear learning. Our data indicate that synaptically released Zn2+ enables long-term potentiation at the cortico-amygdala synapses by depressing feed-forward GABAergic inhibition of principal neurons. This regulatory mechanism, implicating pathway-dependent release of Zn2+, may serve an essential control function in assuring spatial specificity of long-lasting synaptic modifications in the neural circuit of a learned behavior.

We used the patch-clamp technique to identify and characterize the electrophysiological, biophysical, and pharmacological properties of K(+) channels in enzymatically dissociated ventricular cells of the land pulmonate snail Helix. The family of outward K(+) currents started to activate at -30 mV and the activation was faster at more depolarized potentials (time constants: at 0 mV 17.4 +/- 1.2 ms vs. 2.5 +/- 0.1 ms at + 60 mV). The current waveforms were similar to those of the A-type family of voltage-dependent K(+) currents encoded by Kv4.2 in mammals. Inactivation of the current was relatively fast, i.e., 50.2 +/- 1.8% of current was inactivated within 250 ms at + 40 mV. The recovery of K(+) channels from inactivation was relatively slow with a mean time constant of 1.7 +/- 0.2 s. Closer examination of steady-state inactivation kinetics revealed that the voltage dependency of inactivation was U-shaped, exhibiting less inactivation at more depolarized membrane potentials. On the basis of this phenomenon, we suggest that a channel encoded by Kv2.1 similar to that in mammals does exist in land pulmonates of the Helix genus. Outward currents were sensitive to 4-aminopyridine and tetraethylammonium chloride. The last compound was most effective, with an IC(50) of 336 +/- 142 micro mol l(-1). Thus, using distinct pharmacological and biophysical tools we identified different types of voltage-gated K(+) channels.

Overexpression of a truncated Kv1.1 or Kv2.1 channel polypeptide in the heart (Kv1DN or Kv2DN) resulted in mice with a prolonged action potential duration (APD) due to marked attenuation of rapidly activating, slowly inactivating K+ current (I(K,slow1)) or slowly inactivating outward K(+) current (I(K,slow2)) in ventricular myocytes. ECG monitoring, optical mapping, and programmed electrical stimulation of Kv1DN mice revealed spontaneous and inducible reentrant ventricular tachycardia due to spatial dispersion of repolarization and refractoriness. Recently, we demonstrated upregulation of I(K,slow2) in apical cardiomyocytes derived from Kv1DN mice. We therefore hypothesized that the selective upregulation of Kv2.1-encoded currents underlies the apex-to-base dispersion of repolarization and the reentrant arrhythmias. To test this hypothesis, the Kv1DN line was crossbred with the Kv2DN line to produce Kv1/Kv2DN lines. Whole cell voltage-clamp recordings from left ventricular cells of Kv1/Kv2DN confirmed that the 4-aminopyridine- and tetraethylammonium-sensitive components of IK,slow were eliminated, resulting in marked APD prolongation compared with wild-type, Kv1DN, and Kv2DN cells. Telemetric ECG recordings revealed prolongation of the corrected QT in Kv1/Kv2DN compared with Kv1DN and Kv2DN mice. However, attenuation of Kv2.1-encoded currents in Kv1DN mice did not suppress the arrhythmias. Thus, the elimination of I(K,slow2) prolongs APD and the QT intervals, but does not have an antiarrhythmic effect.

Overexpression of a dominant-negative truncated Kv1.1 (Kv1DN) polypeptide in the mouse heart resulted in marked attenuation of a 4-aminopyridine (4-AP)-sensitive current, I(K,slow1). We used recombinant adeno-associated virus (rAAV) as a vector for direct delivery of Kv1.5 into the mouse myocardium in order to normalize the action potential duration (APD) 6 months after injection. The injection of rAAV-Kv1.5 reconstituted the 4-AP-sensitive outward potassium currents, shortened the APD, and eliminated spontaneous early afterdepolarizations. Immunoblots detected the FL-Kv1.5 polypeptides only in rAAV-Kv1.5-infected hearts. These data demonstrate long-term expression of 4-AP-sensitive potassium currents in ventricular myocytes by gene transfer using rAAV vector encodes Kv1.5.

Mutations in cardiac voltage-gated K+ channels cause long QT syndrome (LQTS) and sudden death. We created a transgenic mouse with a long QT phenotype (Kv1DN) by overexpression of a truncated K+ channel in the heart and investigated whether the dominant negative effect of the transgene would be overcome by the direct injection of adenoviral vectors expressing wild-type Kv1.5 (AV-Kv1.5) into the myocardium. End points at 3-10 days included electrophysiology in isolated cardiomyocytes, surface ECG, programmed stimulation of the right ventricle, and in vivo optical mapping of action potentials and repolarization gradients in Langendorff-perfused hearts. Overexpression of Kv1.5 reconstituted a 4-aminopyridine-sensitive outward K+ current, shortened the action potential duration, eliminated early afterdepolarizations, shortened the QT interval, decreased dispersion of repolarization, and increased the heart rate. Each of these changes is consistent with a physiologically significant primary effect of adenoviral expression of Kv1.5 on ventricular repolarization of Kv1DN mice.