Applicability of Fractal Analysis for Quantitative Evaluation of Midpalatal Suture Maturation.

BACKGROUND: The treatment of transversal maxillary deficiency usually aims at skeletal expansion. The treatment option highly depends on the maturation stage of the midpalatal suture (MPS), which may vary between individuals at the same chronological age. Therefore, the individual determination of the MPS maturation is crucial. AIMS: Our aim was to investigate the applicability of fractal analysis for the quantitative evaluation of MPS maturation. METHODS: Nine experienced orthodontists were asked to evaluate the MPS maturation on 51 cone beam computed tomography (CBCT) scans according to the Angelieri classification method. Intra- and inter-examiner reliability was measured using Cohen's Kappa coefficient. The stages were agreed upon according to the results of the examiners with the highest strength of agreement. Fractal analysis was then performed on the CBCTs and the correlation between the fractal dimension values and maturation stages was then evaluated. Optimal fractal dimension cut-off values were determined using a receiver operating characteristic curve. RESULTS: The cut-off point was found at 1.073, at which the use of fractal dimension for predicting MPS maturation showed 100% sensitivity, 93.7% specificity, 9.5% false positive, 0% false negative rate. CONCLUSION: Our results provided further evidence that fractal analysis is a reliable tool to determine MPS maturation stage.

Geometric and Electronic Structural Engineering of Isolated Ni Single Atoms for a Highly Efficient CO2 Electroreduction.

Tuning the coordination environment and geometric structures of single atom catalysts is an effective approach for regulating the reaction mechanism and maximize the catalytic efficiency of single-atom centers. Here, a template-based synthesis strategy is proposed for the synthesis of high-density NiNx sites anchored on the surface of hierarchically porous nitrogen-doped carbon nanofibers (Ni-HPNCFs) with different coordination environments. First-principles calculations and advanced characterization techniques demonstrate that the single Ni atom is strongly coordinated with both pyrrolic and pyridinic N dopants, and that the predominant sites are stabilized by NiN3 sites. This dual engineering strategy increases the number of active sites and utilization efficiency of each single atom as well as boosts the intrinsic activity of each active site on a single-atom scale. Notably, the Ni-HPNCF catalyst achieves a high CO Faradaic efficiency (FECO ) of 97% at a potential of -0.7 V, a high CO partial current density (jCO ) of 49.6 mA cm-2 (-1.0 V), and a remarkable turnover frequency of 24 900 h-1 (-1.0 V) for CO2 reduction reactions (CO2 RR). Density functional theory calculations show that compared to pyridinic-type NiNx , the pyrrolic-type NiN3 moieties display a superior CO2 RR activity over hydrogen evolution reactions, resulting in their superior catalytic activity and selectivity.

Differential resting-state neurophysiological activity associated with game usage patterns and genres in Internet gaming disorder.

We investigated differences in quantitative electroencephalogram (EEG) patterns associated with game usage patterns and genre among patients with Internet gaming disorder (IGD). Data from 140 participants (76 IGD patients and 64 healthy controls) were analysed. The IGD group was divided into subgroups based on game usage patterns (single game [SG] or multiple games [MGs]) and genre (multiplayer online battle arena, first-person shooter [FPS], or massively multiplayer online role-playing game [MMORPG; hereafter, MMG]). A resting-state, eye-closed quantitative EEG was recorded, and the absolute power and coherence of brain waves were analysed. IGD patients who played SGs showed increased beta activity compared with those who played MGs and controls. Increased absolute beta power was significantly associated with higher tendencies towards behavioural inhibition compared with controls. FPS gamers showed increased delta power in the frontal region compared with controls, which was related to the severity of IGD. Furthermore, decreased intrahemispheric coherence in the left frontoparietal region was observed in the MMG and FPS groups compared with controls. This decreased coherence was observed in the theta (MMG and FPS), delta (MMG), and beta (FPS) bands. These features were related to impairment in visuospatial working memory. Unique neurophysiological features related to preoccupation with an SG may be associated with the inhibition of behavioural changes. The present study suggests that the underlying neurophysiological networks in IGD differ according to game usage patterns and genre.

Viscoelastic Separation and Concentration of Fungi from Blood for Highly Sensitive Molecular Diagnostics.

Isolation and concentration of fungi in the blood improves sensitivity of the polymerase chain reaction (PCR) method to detect fungi in blood. This study demonstrates a sheathless, continuous separation and concentration method of candida cells using a viscoelastic fluid that enables rapid detection of rare candida cells by PCR analysis. To validate device performance using a viscoelastic fluid, flow characteristics of 2 µm particles were estimated at different flow rates. Additionally, a mixture of 2 µm and 13 µm particles was successfully separated based on size difference at 100 µl/min. Candida cells were successfully separated from the white blood cells (WBCs) with a separation efficiency of 99.1% and concentrated approximately 9.9-fold at the center outlet compared to the initial concentration (~2.5 × 107 cells/ml). Sequential 1st and 2nd concentration processes were used to increase the final number of candida cells to ~2.3 × 109 cells/ml, which was concentrated ~92-fold. Finally, despite the undetectable initial concentration of 101 CFU/ml, removal of WBCs and the additional buffer solution enabled the quantitative reverse transcription (RT)-PCR detection of candida cells after the 1st concentration (Ct = 31.43) and the 2nd concentration process (Ct = 29.30).

Alterations of voltage-dependent K(+) channels in the mesenteric artery during the early and chronic phases of diabetes.

This study investigated the alteration of voltage-dependent K(+) (Kv) channels in mesenteric arterial smooth muscle cells from control (Long-Evans Tokushima Otsuka [LETO]) and diabetic (Otsuka Long-Evans Tokushima Fatty [OLETF]) rats during the early and chronic phases of diabetes. We demonstrated alterations in the mesenteric Kv channels during the early and chronic phase of diabetes using the patch-clamp technique, the arterial tone measurement system, and RT-PCR in Long-Evans Tokushima (LETO; for control) and Otsuka Long-Evans Tokushima Fatty (OLETF; for diabetes) type 2 diabetic model rats. In the early phase of diabetes, the amplitude of mesenteric Kv currents induced by depolarizing pulses was greater in OLETF rats than in LETO rats. The contractile response of the mesenteric artery induced by the Kv inhibitor, 4-aminopyridine (4-AP), was also greater in OLETF rats. The expression of most Kv subtypes- including Kv1.1, Kv1.2, Kv1.4, Kv1.5, Kv1.6, Kv2.1, Kv3.2, Kv4.1, Kv4.3, Kv5.1, Kv6.2, Kv8.1, Kv9.3, and Kv10.1-were increased in mesenteric arterial smooth muscle from OLETF rats compared with LETO rats. However, in the chronic phase of diabetes, the Kv current amplitude did not differ between LETO and OLETF rats. In addition, the 4-AP-induced contractile response of the mesenteric artery and the expression of Kv subtypes did not differ between the two groups. The increased Kv current amplitude and Kv channel-related contractile response were attributable to the increase in Kv channel expression during the early phase of diabetes. The increased Kv current amplitude and Kv channel-related contractile response were reversed during the chronic phase of diabetes.

The Effects of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on Voltage-Dependent K(+) Channels in Rabbit Coronary Arterial Smooth Muscle Cells.

We demonstrated the inhibitory effect of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), on voltage-dependent K(+) (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Fluvoxamine reduced the amplitude of Kv currents in a concentration-dependent manner with an IC50 value of 3.71±1.09 µM and a Hill coefficient of 0.62±0.14. Although fluvoxamine did not significantly affect the steady-state activation curve, it shifted the steady-state inactivation curve toward a more negative potential. Pretreatment with another SSRI, paroxetine, did not affect the basal Kv current and did not alter the inhibitory effect of fluvoxamine on Kv channels. We concluded that fluvoxamine inhibits the Kv current in a concentration-dependent manner and in a closed (inactivated) state of the Kv channels independent of serotonin reuptake inhibition.

The calmodulin inhibitor CGS 9343B inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.

We investigated the effects of the calmodulin inhibitor CGS 9343B on voltage-dependent K(+) (Kv) channels using whole-cell patch clamp technique in freshly isolated rabbit coronary arterial smooth muscle cells. CGS 9343B inhibited Kv currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC50) value of 0.81µM. The decay rate of Kv channel inactivation was accelerated by CGS 9343B. The rate constants of association and dissociation for CGS 9343B were 2.77±0.04µM(-1)s(-1) and 2.55±1.50s(-1), respectively. CGS 9343B did not affect the steady-state activation curve, but shifted the inactivation curve toward to a more negative potential. Train pulses (1 or 2Hz) application progressively increased the CGS 9343B-induced Kv channel inhibition. In addition, the inactivation recovery time constant was increased in the presence of CGS 9343B, suggesting that CGS 9343B-induced inhibition of Kv channel was use-dependent. Another calmodulin inhibitor, W-13, did not affect Kv currents, and did not change the inhibitory effect of CGS 9343B on Kv current. Our results demonstrated that CGS 9343B inhibited Kv currents in a state-, time-, and use-dependent manner, independent of calmodulin inhibition.

Cilostazol induces vasodilation through the activation of Ca(2+)-activated K(+) channels in aortic smooth muscle.

We investigated the vasorelaxant effect of cilostazol and related signaling pathways in phenylephrine (Phe)-induced pre-contracted aortic rings. Cilostazol induced vasorelaxation in a concentration-dependent manner when aortic rings were pre-contracted with Phe. Application of the voltage-dependent K(+) (Kv) channel inhibitor 4-AP, the ATP-sensitive K(+) (K(ATP)) channel inhibitor glibenclamide, and the inwardly rectifying K(+) (Kir) channel inhibitor Ba(2+) did not alter the vasorelaxant effect of cilostazol; however, pre- and post-treatment with the big-conductance Ca(2+)-activated K(+) (BK(Ca)) channel inhibitor paxilline inhibited the vasorelaxant effect of cilostazol. This vasorelaxant effect of cilostazol was reduced in the presence of an adenylyl cyclase or a protein kinase A (PKA) inhibitor, but not a protein kinase G inhibitor. Inside-out single channel recordings revealed that cilostazol induced the activation of BK(Ca) channel activity. The vasorelaxant effect of cilostazol was not affected by removal of the endothelium. In addition, application of a nitric oxide synthase inhibitor and a small-conductance Ca(2+)-activated K(+) (SK(Ca)) channel inhibitor did not affect cilostazol-induced vasorelaxation. We conclude that cilostazol induced vasorelaxation of the aorta through activation of BK(Ca) channel via a PKA-dependent signaling mechanism independent of endothelium.

W-7 inhibits voltage-dependent K(+) channels independent of calmodulin activity in rabbit coronary arterial smooth muscle cells.

We investigated the effect of W-7, a calmodulin inhibitor, on voltage-dependent K(+) (Kv) channels in freshly isolated coronary arterial smooth muscle cells using the whole-cell patch clamp technique. The amplitude of Kv currents was inhibited by W-7 in a concentration-dependent manner, with an IC50 value of 3.38±0.47µM and a Hill coefficient of 0.84±0.10. W-7 shifted the activation curve to a more positive potential but had no significant effect on the inactivation curve, which indicated that W-7 inhibited the Kv current in a closed state of the Kv channel. Another calmodulin inhibitor, W-13, had no significant effect on Kv currents and did not change the inhibitory effect of W-7 on Kv channels. From these results, we conclude that W-7 inhibited the Kv current in a dose-dependent manner, but this inhibition occurred independent of calmodulin activity and in a closed (inactivated) state of the Kv channels.

Ca2+ channel inhibitor NNC 55-0396 inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.

We demonstrated the inhibitory effect of NNC 55-0396, a T-type Ca(2+) channel inhibitor, on voltage-dependent K(+) (K(V)) channels in freshly isolated rabbit coronary arterial smooth muscle cells. NNC 55-0396 decreased the amplitude of K(V) currents in a concentration-dependent manner, with an IC(50) of 0.080 µM and a Hill coefficient of 0.76.NNC 55-0396 did not affect steady-state activation and inactivation curves, indicating that the compound does not affect the voltage sensitivity of K(V) channel gating. Both the K(V) currents and the inhibitory effect of NNC 55-0396 on K(V) channels were not altered by depletion of extracellular Ca(2+) or intracellular ATP, suggesting that the inhibitory effect of NNC 55-0396 is independent of Ca(2+)-channel activity and phosphorylation-dependent signaling cascades. From these results, we concluded that NNC 55-0396 dosedependently inhibits K(V) currents, independently of Ca(2+)-channel activity and intracellular signaling cascades.

The calmodulin inhibitor and antipsychotic drug trifluoperazine inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.

We investigated the effect of the calmodulin inhibitor and antipsychotic drug trifluoperazine on voltage-dependent K(+) (Kv) channels. Kv currents were recorded by whole-cell configuration of patch clamp in freshly isolated rabbit coronary arterial smooth muscle cells. The amplitudes of Kv currents were reduced by trifluoperazine in a concentration-dependent manner, with an apparent IC50 value of 1.58±0.48 µM. The rate constants of association and dissociation by trifluoperazine were 3.73±0.33 µM(-1) s(-1) and 5.84±1.41 s(-1), respectively. Application of trifluoperazine caused a positive shift in the activation curve but had no significant effect on the inactivation curve. Furthermore, trifluoperazine provoked use-dependent inhibition of the Kv current under train pulses (1 or 2 Hz). These findings suggest that trifluoperazine interacts with Kv current in a closed state and inhibits Kv current in the open state in a time- and use-dependent manner, regardless of its function as a calmodulin inhibitor and antipsychotic drug.

The Ca(2+) channel inhibitor efonidipine decreases voltage-dependent K(+) channel activity in rabbit coronary arterial smooth muscle cells.

The effect of efonidipine, a commercially available antihypertensive drug and Ca(2+) channel inhibitor, on voltage-dependent K(+) (Kv) channels was studied in freshly isolated rabbit coronary arterial smooth muscle cells using the whole-cell patch clamp technique. The amplitude of Kv current was decreased by application of efonidipine in a dose-dependent manner, with IC50 of 0.26µM and a Hill coefficient of 0.91, which suggests 1:1 binding stoichiometry. Efonidipine did not affect voltage-dependent activation of the Kv channel, but shifted the inactivation curve by -8.87mV. The inhibitory effect of efonidipine was not significantly changed by depletion of extracellular Ca(2+) or intracellular ATP, which indicated no involvement of the Ca(2+) channel or intracellular protein kinase-dependent cascades. We conclude that efonidipine dose-dependently inhibits Kv current in a phosphorylation- and Ca(2+) channel-independent manner.

Functional expression of smooth muscle-specific ion channels in TGF-ß(1)-treated human adipose-derived mesenchymal stem cells.

Human adipose tissue-derived mesenchymal stem cells (hASCs) have the power to differentiate into various cell types including chondrocytes, osteocytes, adipocytes, neurons, cardiomyocytes, and smooth muscle cells. We characterized the functional expression of ion channels after transforming growth factor-ß1 (TGF-ß1)-induced differentiation of hASCs, providing insights into the differentiation of vascular smooth muscle cells. The treatment of hASCs with TGF-ß1 dramatically increased the contraction of a collagen-gel lattice and the expression levels of specific genes for smooth muscle including α-smooth muscle actin, calponin, smooth mucle-myosin heavy chain, smoothelin-B, myocardin, and h-caldesmon. We observed Ca(2+), big-conductance Ca(2+)-activated K(+) (BKCa), and voltage-dependent K(+) (Kv) currents in TGF-ß1-induced, differentiated hASCs and not in undifferentiated hASCs. The currents share the characteristics of vascular smooth muscle cells (SMCs). RT-PCR and Western blotting revealed that the L-type (Cav1.2) and T-type (Cav3.1, 3.2, and 3.3), known to be expressed in vascular SMCs, dramatically increased along with the Cavß1 and Cavß3 subtypes in TGF-ß1-induced, differentiated hASCs. Although the expression-level changes of the ß-subtype BKCa channels varied, the major α-subtype BKCa channel (KCa1.1) clearly increased in the TGF-ß1-induced, differentiated hASCs. Most of the Kv subtypes, also known to be expressed in vascular SMCs, dramatically increased in the TGF-ß1-induced, differentiated hASCs. Our results suggest that TGF-ß1 induces the increased expression of vascular SMC-like ion channels and the differentiation of hASCs into contractile vascular SMCs.

The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K(+) channels in rabbit coronary arterial smooth muscle cells.

AIMS: We examined the effect of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, on voltage-dependent K(+) (Kv) channels. MAIN METHODS: Electrophysiological recordings were performed in freshly isolated rabbit coronary arterial smooth muscle cells. KEY FINDINGS: The Kv current amplitude was inhibited by LY294002 in a dose-dependent manner, with a Kd value of 1.48µM. Without alteration of the kinetics of activation, LY294002 accelerated the decay rate of Kv channel inactivation. The rate constants of association and dissociation for LY294002 were 1.83±0.01µM(-1)s(-1) and 2.59±0.14s(-1), respectively. Application of LY294002 had no significant impact on the steady-state activation or inactivation curves. In the presence of LY294002, the recovery time constant from inactivation was increased, and Kv channel inhibition increased under train pulses (1 or 2Hz). This indicates that LY294002-induced Kv channel inhibition is use-dependent. Furthermore, pretreatment with another PI3K inhibitor, wortmannin (10µM), did not affect the Kv current, and did not change the inhibitory effect of LY294002. SIGNIFICANCE: Based on these results, we suggest that LY294002 directly blocks Kv current irrespective of PI3K inhibition.

The inhibitory effect of curcumin on voltage-dependent K⁺ channels in rabbit coronary arterial smooth muscle cells.

We investigated the effects of curcumin, the principal active compound of turmeric, on voltage-dependent K(+) (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using the voltage-clamp technique. Curcumin reduced the Kv current in a dose-dependent manner with an apparent K(d) value of 1.07 ± 0.03 µM. Although curcumin did not alter the kinetics of Kv current activation, it predominantly accelerated the decay rate of channel inactivation. The association and dissociation rate constants of curcumin were 1.35 ± 0.05 µM(-1)s(-1) and 1.47 ± 0.17s(-1), respectively. Curcumin did not alter the steady-state activation or inactivation curves. Application of train pulses (1 or 2 Hz) increased curcumin-induced blockade of the Kv current, and the recovery time constant also increased in the presence of curcumin suggesting, that the inhibitory action of Kv currents by curcumin was use-dependent. From these results, we concluded that curcumin inhibited vascular Kv current in a state-, time-, and use-dependent manner.

The T-type Ca²âº channel inhibitor mibefradil inhibits voltage-dependent K⁺ channels in rabbit coronary arterial smooth muscle cells.

We examined the effects of mibefradil, a T-type Ca²âº channel inhibitor, on voltage-dependent K⁺ (Kv) channels in rabbit coronary arterial smooth muscle cells using the whole-cell patch clamp technique. Mibefradil reduced the Kv current amplitude in a dose-dependent manner, with an apparent K(d) value of 1.08 µM. Kv current inhibition by mibefradil was highly voltage-dependent over the full activation voltage range (-30 to +10 mV). The decay rate of Kv channel inactivation was accelerated by mibefradil without altering the kinetics of current activation. The rate constants of association and dissociation were 2.23 ± 0.07 µM⁻¹·s⁻¹ and 2.40 ± 0.42 s⁻¹, respectively. Mibefradil had no significant effect on the steady-state activation or inactivation curves. In the presence of mibefradil, the recovery time constant from inactivation was decreased, and the application of train pulses (1 or 2 Hz) increased mibefradil-induced Kv channel inhibition, suggesting that the inhibitory effects of mibefradil were use-dependent. The inhibitory effect of mibefradil on Kv channels was unaffected by extracellular Ca²âº-free conditions. Moreover, the absence of ATP inside the pipette did not alter the blocking effect of mibefradil. Therefore, we suggest that mibefradil directly inhibited the Kv current, independently of Ca²âº channel inhibition.

The inhibitory effect of BIM (I) on L-type Ca²âº channels in rat ventricular cells.

We investigated the effect of a specific protein kinase C (PKC) inhibitor, bisindolylmaleimide I [BIM (I)], on L-type Ca(2+) channels in rat ventricular myocytes. BIM (I) alone inhibited the L-type Ca(2+) current in a concentration-dependent manner, with a K(d) value of 3.31 ± 0.25 µM, and a Hill coefficient of 2.34 ± 0.23. Inhibition was immediate after applying BIM (I) in the bath solution and then it partially washed out. The steady-state activation curve was not altered by applying 3µ M BIM (I), but the steady-state inactivation curve shifted to a more negative potential with a change in the slope factor. Other PKC inhibitors, PKC-IP and chelerythrine, showed no significant effects either on the L-type Ca(2+) current or on the inhibitory effect of BIM (I) on the L-type Ca(2+) current. The results suggest that the inhibitory effect of BIM (I) on the L-type Ca(2+) current is independent of the PKC pathway. Thus, our results should be considered in studies using BIM (I) to inhibit PKC activity and ion channel modulation.

Alteration of ATP-sensitive K+ channels in rabbit aortic smooth muscle during left ventricular hypertrophy.

We investigated the impairment of ATP-sensitive K(+) (K(ATP)) channels in aortic smooth muscle cells (ASMCs) from isoproterenol-induced hypertrophied rabbits. The amplitude of K(ATP) channels induced by the K(ATP) channel opener pinacidil (10 µM) was greater in ASMCs from control than from hypertrophied animals. In phenylephrine-preconstricted aortic rings, pinacidil induced relaxation in a dose-dependent manner. The dose-dependent curve was shifted to the right in the hypertrophied (EC(50): 17.80 ± 3.28 µM) compared with the control model (EC(50): 6.69 ± 2.40 µM). Although the level of Kir6.2 subtype expression did not differ between ASMCs from the control and hypertrophied models, those of the Kir6.1 and SUR2B subtypes were decreased in the hypertrophied model. Application of the calcitonin-gene related peptide (100 nM) and adenylyl cyclase activator forskolin (10 µM), which activates protein kinase A (PKA) and consequently K(ATP) channels, induced a K(ATP) current in both control and hypertrophied animals; however, the K(ATP) current amplitude did not differ between the two groups. Furthermore, PKA expression was not altered between the control and hypertrophied animals. These results suggests that the decreased K(ATP) current amplitude and K(ATP) channel-induced vasorelaxation in the hypertrophied animals were attributable to the reduction in K(ATP) channel expression but not to changes in the intracellular signaling mechanism that activates the K(ATP) current.

Direct effect of protein kinase C inhibitors on cardiovascular ion channels.

Protein kinase C (PKC) is a central enzyme that modulates numerous biological functions. For this reason, specific PKC inhibitors/ activators are required to study PKC-related signaling mechanisms. To date, although many PKC inhibitors have been developed, they are limited by poor selectivity and nonspecificity. In this review, we focus on the nonspecific actions of PKC inhibitors on cardiovascular ion channels in addition to their PKC-inhibiting functions. The aim of this paper is to urge caution when using PKC inhibitors to block PKC function. This information may help to better understand PKC-related physiological/biochemical studies.

A Carbohydrate Fraction, AIP1, from Artemisia Iwayomogi Reduces the Action Potential Duration by Activation of Rapidly Activating Delayed Rectifier K Channels in Rabbit Ventricular Myocytes.

We investigated the effects of a hot-water extract of Artemisia iwayomogi, a plant belonging to family Compositae, on cardiac ventricular delayed rectifier K(+) current (I(K)) using the patch clamp technique. The carbohydrate fraction AIP1 dose-dependently increased the heart rate with an apparent EC(50) value of 56.1+/-5.5 microg/ml. Application of AIP1 reduced the action potential duration (APD) in concentration-dependent fashion by activating I(K) without significantly altering the resting membrane potential (IC(50) value of APD(50): 54.80+/-2.24, IC(50) value of APD(90): 57.45+/-3.47 microg/ml). Based on the results, all experiments were performed with 50 microg/ml of AIP1. Pre-treatment with the rapidly activating delayed rectifier K(+) current (I(Kr)) inhibitor, E-4031 prolonged APD. However, additional application of AIP1 did not reduce APD. The inhibition of slowly activating delayed rectifier K(+) current (I(Ks)) by chromanol 293B did not change the effect of AIP1. AIP1 did not significantly affect coronary arterial tone or ion channels, even at the highest concentration of AIP1. In summary, AIP1 reduces APD by activating I(Kr) but not I(Ks). These results suggest that the natural product AIP1 may provide an adjunctive therapy of long QT syndrome.