Modulation Of Channel Currents Research Articles

A scalable top-gate graphene field effect transistor with a polydimethylsiloxane dielectric

The limitations of modern CMOS technology have created a call to action for novel devices with great scalability potential. Graphene has been recognized as a suitable material for an enhanced transistor channel based on its incredibly large conductivity while also being easily scaled. Previous research has noted the importance of a top gate device structure, which is difficult to accomplish for graphene transistors due to graphene's incompatibility with oxide growth processes. A novel process flow for graphene field effect transistors with scalability is presented. The emphasis is on the growth of multilayer graphene using chemical vapor deposition and the implementation of polydimethylsiloxane as a gate dielectric. Polydimethylsiloxane gate insulator thickness of 815 nm and 570 nm were successfully developed on 4in large-scale wafers. Two devices of similar channel dimensions and different dielectric were compared and mobilities of 14.57cm2V−1s−1 and 0.44 cm2V−1s−1 were measured. Gate voltage sweeps from -20 V to 20 V also demonstrated channel current modulation with a charge neutrality point between 5 V and 8 V, indicating achievement of expected device operation.

WOx channel engineering of Cu-ion-driven synaptic transistor array for low-power neuromorphic computing

The multilevel current states of synaptic devices in artificial neural networks enable next-generation computing to perform cognitive functions in an energy-efficient manner. Moreover, considering large-scale synaptic arrays, multiple states programmed in a low-current regime may be required to achieve low energy consumption, as demonstrated by simple numerical calculations. Thus, we propose a three-terminal Cu-ion-actuated CuOx/HfOx/WO3 synaptic transistor array that exhibits analogously modulated channel current states in the range of tens of nanoamperes, enabled by WO3 channel engineering. The introduction of an amorphous stoichiometric WO3 channel formed by reactive sputtering with O gas significantly lowered the channel current but left it almost unchanged with respect to consecutive gate voltage pulses. An additional annealing process at 450 °C crystallized the WO3, allowing analog switching in the range of tens of nanoamperes. The incorporation of N gas during annealing induced a highly conductive channel, making the channel current modulation negligible as a function of the gate pulse. Using this optimized gate stack, Poole–Frenkel conduction was identified as a major transport characteristic in a temperature-dependent study. In addition, we found that the channel current modulation is a function of the gate current response, which is related to the degree of progressive movement of the Cu ions. Finally, the synaptic characteristics were updated using fully parallel programming and demonstrated in a 7 × 7 array. Using the CuOx/HfOx/WO3 synaptic transistors as weight elements in multilayer neural networks, we achieved a 90% recognition accuracy on the Fashion-MNIST dataset.

Modulation of Kv7 Channel Currents by Echinocystic Acid.

Modulation of KCNQ-encoded voltage-gated potassium Kv7/M channel function represents an attractive strategy to treat neuronal excitability disorders such as epilepsy, pain, and depression. The Kv7 channel group includes five subfamily members (Kv7.1-7.5). Pentacyclic triterpenes display extensive pharmacological activities including anti-tumor, anti-inflammatory, and anti-depression effects. In this study, we investigated the effects of pentacyclic triterpenes on Kv7 channels. Our results show that echinocystic acid, ursonic acid, oleanonic acid, demethylzeylasteral, corosolic acid, betulinaldehyde, acetylursolic acid, and ⍺-boswellic acid gradually exert decreasing degrees of Kv7.2/Kv7.3 channel current inhibition. Echinocystic acid was the most potent inhibitor, with a half-maximal inhibitory concentration (IC50) of 2.5 µM. It significantly shifted the voltage-dependent activation curve in a positive direction and slowed the time constant of activation for Kv7.2/Kv7.3 channel currents. Furthermore, echinocystic acid non-selectively inhibited Kv7.1-Kv7.5 channels. Taken together, our findings indicate that echinocystic acid is a novel and potent inhibitor that could be used as a tool to further understand the pharmacological functions of neuronal Kv7 channels. Significance Statement Pentacyclic triterpenes reportedly have multiple potential therapeutic uses such as anticancer, anti-inflammatory, antioxidant, and anti-depression effects. In the present study, we show that echinocystic acid, ursonic acid, oleanonic acid, and demethylzeylasteral inhibit Kv7.2/Kv7.3 channels to varying degrees. Of these, echinocystic acid was the most potent Kv7.2/Kv7.3 current inhibitor and inhibited Kv7.1-Kv7.5 currents in a non-selective manner.

Pushing On-Chip Photosensitivity Forward Using Edge-Driven Vertical Organic Phototransistors

Developing high-performance photosensors using prototype device architectures is essential to pushing forward developing and advancing next-generation optoelectronic applications. This work reports an organic phototransistor (OPT) with an ultra-short conducting channel (tens of nanometers) and outstanding photoelectric conversion efficiency. The OPT is based on a vertical organic field-effect transistor (VOFET) architecture, which utilizes a rolled-up metallic nanomembrane (NM) as the drain electrode and a photolithographically patterned (rectangular-shaped) perforated source electrode. These features expand the concept of conventional VOFETs as the former enables the incorporation of ultra-thin active layers and allows reliable control over gate-induced modulation of channel current. Using the engineering as abovementioned strategies, we focused on obtaining an improved device performance, studying their fundamental operating principle, and further investigating their application as photosensors. The optimized devices exhibited low operating voltages (<5 V) and enhanced on/off current ratio (∼105). The VOFET photoresponse was characterized by measuring the electrical characteristics in the dark and under illumination using three different monochromatic light colors. Under blue light, our devices demonstrated impressive photosensitivity (Pmax ≈ 105) and fast photoelectric conversion (steep light-induced threshold voltage shift), demonstrating that the rolled-up NM OPT shows excellent potential as a highly sensitive photodetector with low power consumption.

Highly Reliable Physical Bending Sensors using Heterostructured Floating Gate Organic Transistor

AbstractHerein, a piezovoltage‐modulated field‐effect transistor (PVMFET) is proposed that provides physical sensing capabilities while maintaining excellent FET performance through the combination of a piezovoltage (PV) capacitor sensing medium and an FET structure that can amplify signal responses to external stimuli. The PV generated in the piezoelectric poly(vinylidene fluoride)‐co‐trifluoroethylene‐based PV capacitor through bending deformation modulates the effective gate voltage induced in the PV‐modulated gate. In particular, in the device, it is found that the piezo‐responsive modulation of the effective gate electric field is enhanced by the applied gate voltage, corresponding to the higher modulation of channel current at the higher gate voltage under bending. Accordingly, a PVMFET‐based physical sensor that can accurately estimate the bending angle is implemented. The sensor exhibits a high sensitivity, repeatability, and a sensing linearity of 0.98 while the bending angle is varied from 0° to 93°. The sensing performance remains constant even when the bending frequency changed from 0.25 to 1.0 Hz at the largest bending angle (93°) measured, confirming the effectiveness of the sensor platform. The proposed PVMFET‐based physical sensor platform is suitable for applications that require stable driving performance and the simultaneous detection of external physical stimuli in real time.

Study of electrical transport properties of GaN-based side-gate heterostructure transistors

In this study, GaN-based side-gate heterostructure transistors (SGHTs) with two electrical operating modes were fabricated. In the first operating mode, the SGHT was utilized as a common-source voltage amplifier with low power consumption and a broad input signal range. Analysis of the main scattering mechanisms affecting the electrical transport of two-dimensional electron gas (2DEG) in the channel revealed that polar optical phonon scattering and polarization Coulomb field (PCF) scattering play dominant roles under different side-gate voltages. In addition, channel current modulation of 2DEG electron mobility is primarily attributed to PCF scattering. Due to PCF scattering, the channel width also modulates the threshold voltage in this mode of operation. Moreover, in the second operating mode, the SGHT functioned as a traditional GaN high electron mobility transistor, allowing for electrically modulated threshold voltage and transconductance.

Structural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277

The KCNQ1 ion channel plays critical physiological roles in electrical excitability and K+ recycling in organs including the heart, brain, and gut. Loss of function is relatively common and can cause sudden arrhythmic death, sudden infant death, epilepsy and deafness. Here, we report cryogenic electron microscopic (cryo-EM) structures of Xenopus KCNQ1 bound to Ca2+/Calmodulin, with and without the KCNQ1 channel activator, ML277. A single binding site for ML277 was identified, localized to a pocket lined by the S4-S5 linker, S5 and S6 helices of two separate subunits. Several pocket residues are not conserved in other KCNQ isoforms, explaining specificity. MD simulations and point mutations support this binding location for ML277 in open and closed channels and reveal that prevention of inactivation is an important component of the activator effect. Our work provides direction for therapeutic intervention targeting KCNQ1 loss of function pathologies including long QT interval syndrome and seizures.

Two-Dimensional CIPS-InSe van der Waal Heterostructure Ferroelectric Field Effect Transistor for Nonvolatile Memory Applications.

Channel current conduction modulation with the spontaneous polarization of ferroelectric films in ferroelectric field-effect transistors (FeFETs) has been widely investigated. Low interface quality and thermodynamic instability owing to the presence of dangling bonds in the conventional ferroelectrics have limited the memory retention and endurance of FeFETs. This, in turn, prevents their commercialization. However, the atomically thin nature of 2D ferroelectric, semiconducting, and insulating films facilitate the achievement of trap-free interfaces as van der Waal heterostructures (vdWHs) to develop FeFETs with long data retention and endurance characteristics. Here, we demonstrate a 2D vdWH FeFET fabricated with ferroelectric CuInP2S6 (CIPS), hexagonal boron nitride (h-BN) as the dielectric, and InSe as the ferroelectric semiconductor channel. The device shows an excellent performance as nonvolatile memory (NVM) with its large memory window (4.6 V at a voltage sweep of 5 V), high drain current on/off ratio (>104), high endurance, and long data retention (>104 s). These results demonstrate the considerable potential of vdWHs for the development of FeFETs for logic and NVM applications.

Deep Proton Insertion Assisted by Oxygen Vacancies for Long‐Term Memory in VO2 Synaptic Transistor

AbstractReversible phase transformation of correlated oxides by field‐driven ionic process present opportunity to efficiently transduce between ionic transfer and electrical currents in insertion‐based reconfigurable transistors. However, the switching rate of insertion transistors is fundamentally limited by the slow rate of ionic insertion into the lattices of correlated oxides. Here, it is demonstrated that preformed oxygen vacancies in VO2−δ lattices strongly accelerate proton insertion by low gate voltage in synaptic transistors. As the degree of oxygen deficiency δ increases in VO2−δ transistors, the steepness of phase transformation and transconductance increase during the voltage sweep at the expense of the channel current modulation. Theoretical and experimental analyses reveal that the accelerated of H+ kinetics in the VO2−δ lattice occurs because immobile oxygen vacancies reduce the energy barrier to H+ migration. In an electronic synapse, this facile H+ migration in VO2−δ lattices renders “inscribed” memory by positioning the H+ neurotransmitter far from the electrolyte/VO2−δ interface. This discovery suggests a strategy to improve the learning and memory processes of artificial synaptic devices by controlling the density of intrinsic defects in the lattice framework to achieve efficient ion exchange.

Rapid Photonic Processing of High-Electron-Mobility PbS Colloidal Quantum Dot Transistors.

Recent advances in solution-processable semiconducting colloidal quantum dots (CQDs) have enabled their use in a range of (opto)electronic devices. In most of these studies, device fabrication relied almost exclusively on thermal annealing to remove organic residues and enhance inter-CQD electronic coupling. Despite its widespread use, however, thermal annealing is a lengthy process, while its effectiveness to eliminate organic residues remains limited. Here, we exploit the use of xenon flash lamp sintering to post-treat solution-deposited layers of lead sulfide (PbS) CQDs and their application in n-channel thin-film transistors (TFTs). The process is simple, fast, and highly scalable and allows for efficient removal of organic residues while preserving both quantum confinement and high channel current modulation. Bottom-gate, top-contact PbS CQD TFTs incorporating SiO2 as the gate dielectric exhibit a maximum electron mobility of 0.2 cm2 V–1 s–1, a value higher than that of control transistors (≈10–2 cm2 V–1 s–1) processed via thermal annealing for 30 min at 120 °C. Replacing SiO2 with a polymeric dielectric improves the transistor’s channel interface, leading to a significant increase in electron mobility to 3.7 cm2 V–1 s–1. The present work highlights the potential of flash lamp annealing as a promising method for the rapid manufacture of PbS CQD-based (opto)electronic devices and circuits.

High-Current Perovskite Oxide BaTiO3/BaSnO3 Heterostructure Field Effect Transistors

High-current molecular beam epitaxial perovskite oxide semiconductor BaTiO3/BaSnO3 heterostructure field effect transistors on SrTiO3 substrates were developed. Record high current density of $\text{I}_{{\mathrm{max}}} =406.7$ mA/mm, maximum transconductance $\text{g}_{{{\text {m}}}} =72.3$ mS/mm were achieved in a field effect transistor with gate length $\text{L}_{{{\text {g}}}} = 0.64\,\,\mu \text{m}$ , and source-drain spacing $\text{L}_{{{\text {sd}}}} = 3.5\,\,\mu \text{m}$ . The device has a low threshold voltage of $\text{V}_{{{\text {th}}}}= - 4.5$ V and the capability to modulate $5.7\times 10^{{{{13}}}}$ cm $^{{-{2}}}$ electron density in the BaSnO3 channel. The high channel current and gate modulation efficiency are attributed to the high mobility and charge density in the BaSnO3 channel and the utilization of high-k BaTiO3 ( $\varepsilon $ is in the range of 425 and 387 as the electric field increases from 46 to 85 kV/cm) layer as the gate dielectric for charge modulation. Though the device suffers from low current ON/OFF ratio and a large subthreshold swing due to the gate leakage resulted from threading dislocations, this work demonstrates the great potential of perovskite semiconductors for electronic device applications.

Capsazepine prolongation of the duration of lidocaine block of sensory transmission in mice may be mediated by modulation of HCN channel currents.

Background and objectivesHyperpolarization-activation cyclic nucleotide-gated (HCN) channels contribute to the effects of lidocaine. Capsazepine (CPZ), a competitive inhibitor of capsaicin of transient receptor potential vanilloid-1 channel, has also been found to inhibit HCN channel currents (Ih). This study was designed to investigate whether CPZ could prolong durations of lidocaine in regional anesthesia.MethodsMouse HCN1 and HCN2 channels were expressed in human embryonic kidney 293 (HEK 293) cells. The effect of CPZ on Ih was measured by whole-cell patch-clamping recording. Sciatic nerve block model in mice was used for the study in vivo. The mice were randomly divided into seven groups, respectively, receiving lidocaine, CPZ, ZD7288 (HCN channel blocker), CPZ + lidocaine, ZD7288 + lidocaine, ZD7288 + CPZ + lidocaine, forskolin (an activator of adenylyl cyclase) + CPZ + lidocaine. Regional anesthetic durations of lidocaine were determined. Voltage-gated sodium channel currents (INa) and Ih were recorded in dorsal root ganglion neurons of mice. The effects of CPZ on INa and Ih with or without Cyclic adenosine monophosphate (cAMP) were assessed. Isolated mice sciatic nerve was prepared to evaluate the effect of CPZ on the compound action potentials (CAP).ResultsCapsazepine non-selectively inhibited transfected mHCN1 and mHCN2 channel currents in HEK 293 cells. In sciatic nerve block in vivo, compared to lidocaine alone, adding CPZ extended the durations of lidocaine for noxious sensory block (35.1 ± 3.3 vs. 20.3 ± 1.7 min), tactile sensory block (25.5 ± 4.4 vs. 20.0 ± 3.7 min), thermal sensory block (39.6 ± 6.6 vs. 26.8 ± 5.5 min), and motor function block (28.6 ± 4.1 vs. 20.9 ± 4.2 min). Duration of thermal sensory block was longer in CPZ + lidocaine group than that of ZD7288 + lidocaine group (39.6 ± 6.6 vs. 33.4 ± 4.5 min). Forskolin reversed the prolongation by CPZ on lidocaine durations. CPZ or ZD7288 alone did not produce typical regional anesthetic effects. Increased intracellular concentration of cAMP reversed the inhibition of CPZ on Ih. Although CPZ alone inhibited INa at the concentration more than 30 μM, it did not inhibit the CAP amplitudes in isolated sciatic nerves. CPZ dose-dependently enhanced the inhibitory effect of 1% lidocaine on the CAP amplitudes.ConclusionsCapsazepine may prolong durations of lidocaine in peripheral nerve block by modulation of HCN channel currents.

Zoledronic Acid Modulation of TRPV1 Channel Currents in Osteoblast Cell Line and Native Rat and Mouse Bone Marrow-Derived Osteoblasts: Cell Proliferation and Mineralization Effect.

Bisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast/osteoclast ratio. The behavior of ion channels in the presence of BPs is not known. To investigate this, the effect of zoledronic acid BP (ZOL) (3 × 10−8 to 5 × 10−4 M) treatment, on ion channels, cell proliferation, and mineralization, has been investigated on preosteoclast-like cells, RAW264.7, preosteoblast-like cells MC3T3-E1, and rat/mouse native bone marrow-derived osteoblasts. In whole-cell patch clamp on cell line- and bone marrow-derived osteoblasts, ZOL potentiated outward currents. On RAW264.7, ZOL (10−4 M)-evoked current was reduced by the Kv channel blocker tetraethylammonium hydrochloride (TEA), but not by the selective TRPV1-channel antagonist capsazepine. On MC3T3-E1 cells and bone marrow-derived osteoblasts, ZOL-evoked current (5 × 10−8 to 10−4 M) was reduced by capsazepine, whereas the selective TRPV1-channel agonist capsaicin potentiated the control current. In the cell proliferation assay, 72 h incubation of RAW264.7 and MC3T3-E1 cells with ZOL reduced proliferation, with IC50 values of 2.62 × 10−7 M and 2.02 × 10−5 M, respectively. Mineralization of MC3T3-E1 cells and bone marrow-derived osteoblasts was observed in the presence of capsaicin and ZOL (5 × 10−8–10−7 M); ZOL effects were antagonized by capsazepine. In summary, the ZOL-induced activation of TRPV1 channel mediates the mineralization of osteoblasts and counterbalances the antiproliferative effects, increasing the IC50. This mechanism is not operative in osteoclasts lacking the TRPV1 channel.

Effects of Modulation of Ion Channel Currents by Salidroside in H9C2 Myocardial Cells in Hypoxia and Reoxygenation.

Salidroside, a phenyl-propanoid glycoside isolated from the medicinal plant Rhodiola rosea, has potent cardioprotective effects, especially against myocardial hypoxia and reoxygenation injury. However, the molecular mechanism underlying its action is still unclear. The aim of this study was to determine the effect of salidroside on sodium channel current (INa) and transient outward potassium channel current (Ito) in H9C2 cardiomyocytes. H9C2 cells were subcultured under anoxic conditions to mimic myocardial hypoxia and subsequently treated with salidroside. Whole cell patch clamp was performed to determine the effect of hypoxia/reoxygenation and salidroside on myocardial electrophysiological properties. In the differentiated H9C2 cells, hypoxia/reoxygenation reduced INa and Ito amplitude, while salidroside significantly restored both and altered the INa and Ito activation/inactivation kinetics in a dose-dependent manner. Our findings demonstrate that salidroside protects myocardial cells against hypoxia-reoxygenation by restoring the function of sodium and potassium channels.

The L-type calcium channel current modulation mechanism: the plot thickens and fogs.

Stressful situations provoke the fight-or-flight response, incurring rapid elevation of cardiac output via activation of protein kinase A (PKA). In this issue of the JCI, Yang et al. focus on the L-type calcium channel complex (LTCC), and their findings require reexamination of dogmatic principles. LTCC phosphorylation sites identified and studied to date are dispensable for PKA modulation of LTCC; however, a CaVβ2-CaV1.2 calcium channel interaction is now shown to be required. Yang et al. suggest a new hypothesis that LTCC modulation involves rearrangement of auxiliary proteins within the LTCC. However, we still do not know the targets of PKA that mediate LTCC modulation.

Modulation of Abnormal Sodium Channel Currents in Heart and Brain: Hope for SUDEP Prevention and Seizure Reduction.

Modulation of Abnormal Sodium Channel Currents in Heart and Brain: Hope for SUDEP Prevention and Seizure Reduction.

Hydrogen-terminated diamond vertical-type metal oxide semiconductor field-effect transistors with a trench gate

The hydrogen-terminated diamond surface (C-H diamond) has a two-dimensional hole gas (2DHG) layer independent of the crystal orientation. A 2DHG layer is ubiquitously formed on the C-H diamond surface covered by atomic-layer-deposited-Al2O3. Using Al2O3 as a gate oxide, C-H diamond metal oxide semiconductor field-effect transistors (MOSFETs) operate in a trench gate structure where the diamond side-wall acts as a channel. MOSFETs with a side-wall channel exhibit equivalent performance to the lateral C-H diamond MOSFET without a side-wall channel. Here, a vertical-type MOSFET with a drain on the bottom is demonstrated in diamond with channel current modulation by the gate and pinch off.

Dopamine D1 receptor modulation of calcium channel currents in horizontal cells of mouse retina.

Horizontal cells form the first laterally interacting network of inhibitory interneurons in the retina. Dopamine released onto horizontal cells under photic and circadian control modulates horizontal cell function. Using isolated, identified horizontal cells from a connexin-57-iCre × ROSA26-tdTomato transgenic mouse line, we investigated dopaminergic modulation of calcium channel currents (ICa) with whole cell patch-clamp techniques. Dopamine (10 μM) blocked 27% of steady-state ICa, an action blunted to 9% in the presence of the L-type Ca channel blocker verapamil (50 μM). The dopamine type 1 receptor (D1R) agonist SKF38393 (20 μM) inhibited ICa by 24%. The D1R antagonist SCH23390 (20 μM) reduced dopamine and SKF38393 inhibition. Dopamine slowed ICa activation, blocking ICa by 38% early in a voltage step. Enhanced early inhibition of ICa was eliminated by applying voltage prepulses to +120 mV for 100 ms, increasing ICa by 31% and 11% for early and steady-state currents, respectively. Voltage-dependent facilitation of ICa and block of dopamine inhibition after preincubation with a Gβγ-blocking peptide suggested involvement of Gβγ proteins in the D1R-mediated modulation. When the G protein activator guanosine 5'-O-(3-thiotriphosphate) (GTPγS) was added intracellularly, ICa was smaller and showed the same slowed kinetics seen during D1R activation. With GTPγS in the pipette, additional block of ICa by dopamine was only 6%. Strong depolarizing voltage prepulses restored the GTPγS-reduced early ICa amplitude by 36% and steady-state ICa amplitude by 3%. These results suggest that dopaminergic inhibition of ICa via D1Rs is primarily mediated through the action of Gβγ proteins in horizontal cells.

Activity-Dependent Subcellular Cotrafficking of the Small GTPase Rem2 and Ca2+/CaM-Dependent Protein Kinase IIα

BackgroundRem2 is a small monomeric GTP-binding protein of the RGK family, whose known functions are modulation of calcium channel currents and alterations of cytoskeletal architecture. Rem2 is the only RGK protein found predominantly in the brain, where it has been linked to synaptic development. We wished to determine the effect of neuronal activity on the subcellular distribution of Rem2 and its interacting partners.ResultsWe show that Rem2 undergoes activity-and N-Methyl-D-Aspartate Receptor (NMDAR)-dependent translocation in rat hippocampal neurons. This redistribution of Rem2, from a diffuse pattern to one that is highly punctate, is dependent on Ca2+ influx, on binding to calmodulin (CaM), and also involves an auto-inhibitory domain within the Rem2 distal C-terminus region. We found that Rem2 can bind to Ca2+/CaM-dependent protein kinase IIα (CaMKII) a in Ca2+/CaM-dependent manner. Furthermore, our data reveal a spatial and temporal correlation between NMDAR-dependent clustering of Rem2 and CaMKII in neurons, indicating co-assembly and co-trafficking in neurons. Finally, we show that inhibiting CaMKII aggregation in neurons and HEK cells reduces Rem2 clustering, and that Rem2 affects the baseline distribution of CaMKII in HEK cells.ConclusionsOur data suggest a novel function for Rem2 in co-trafficking with CaMKII, and thus potentially expose a role in neuronal plasticity.

Phenylephrine preconditioning involves modulation of cardiac sarcolemmal K ATP current by PKC delta, AMPK and p38 MAPK

Preconditioning of hearts with the α 1-adrenoceptor agonist phenylephrine decreases infarct size and increases the functional recovery of the heart following ischaemia–reperfusion. However, the cellular mechanisms responsible for this protection are not known. We investigated the role of protein kinase C ε and δ (PKCε and PKCδ), AMP-activated protein kinase (AMPK), p38 MAPK (p38) and sarcolemmal ATP-sensitive potassium ( sarcK ATP) channels in phenylephrine preconditioning using isolated rat ventricular myocytes. Preconditioning of ventricular myocytes with phenylephrine increased the recovery of contractile activity following metabolic inhibition and re-energisation from 30.1 ± 1.9% to 66.5 ± 5.2% (P < 0.01) and increased the peak sarcK ATP current activated during metabolic inhibition from 32.1 ± 1.8 pA/pF to 46.0 ± 5.0 pA/pF (P < 0.05), which was required for protection. Phenylephrine preconditioning resulted in a sustained activation of PKCε and PKCδ, and transient activation of AMPK, which was dependent upon activation of PKCδ but not PKCε. P38 was also activated by phenylephrine preconditioning and this was blocked by inhibitors of PKCε, PKCδ or AMPK. Inhibition of PKCδ, AMPK or p38 was sufficient to prevent the increase in current, suggesting that these kinases are involved in modulation of sarcK ATP channel current by phenylephrine preconditioning. However, whilst inhibition of AMPK and p38 prevented the protection from phenylephrine preconditioning, PKCδ inhibition paradoxically had no effect. The increase in sarcK ATP current induced by phenylephrine preconditioning requires PKCδ, AMPK and p38 and may contribute to the observed improvement in contractile recovery.