Microstructural Changes in the Cerebral White Matter After 12 Months of CPAP Treatment for Moderate to Severe Obstructive Sleep Apnoea: A TBSS Study.

Introduction: Continuous positive airway pressure (CPAP) therapy improves clinical symptoms in patients with obstructive sleep apnea (OSA); however, the mechanism of this clinical improvement and how it may be associated with the restoration of white matter (WM) structures in the brain is unclear. Therefore, this study investigated the relationship between the structural recovery of brain WM and improvements in cognitive function and emotion after long-term (12 months) CPAP treatment in patients with OSA. Methods: We collected data from 17 patients with OSA before and 12 months after CPAP treatment, including sleep monitoring, clinical assessment, and diffusion tensor imaging (DTI) magnetic resonance imaging. Results: We observed a partial reversible recovery of brain WM (mean and radial diffusion coefficients) after treatment. This recovery involved the commissural fibers (cingulum, body of corpus callosum), projection fibers (retrolenticular part of the internal capsule, posterior thalamic radiation, posterior limb of the internal capsule, superior corona radiata, posterior corona radiata), association fibers (external capsule, superior longitudinal fasciculus, inferior longitudinal fasciculus), and other regions. In addition, the improvements in WM fibers in one part of the brain significantly were correlated with the Hamilton Anxiety Scale and Hamilton Depression Scale scores. Discussion: Our results suggest that reversible recovery of reduced brain WM integrity due to OSA may require longer CPAP treatment. Moreover, changes in the integrity of the commissural fibers were associated with emotion regulation. These restored WM areas may explain the cognitive and mood improvements observed after OSA treatment.

Acute Changes in the Resting Brain Networks in Concussion Patients: Small-World Topology Perspective.

BACKGROUND: The acute changes that occur in the small-world topology of the brain in concussion patients remain unclear. Here, we investigated acute changes in the small-world organization of brain networks in concussion patients and their influence on persistent post-concussion symptoms. METHODS: Eighteen concussion patients and eighteen age-matched controls were enrolled in this study. All participants underwent computed tomography, magnetic resonance imaging (MRI), susceptibility weighted imaging, and blood oxygen level-dependent functional MRI. A complex network analysis method based on graph theory was used to calculate the parameters of small-world networks under different degrees of network sparsity. All subjects were evaluated using the Glasgow Coma Scale and Rivermead Postconcussion Symptom Questionnaire. RESULTS: Compared with the controls, the normalized cluster coefficient (γ) of whole brain networks in patients and the "small-world" index (σ) was slightly enhanced, whereas the standardized minimum path (λ) was slightly shorter. Whole brain effect (Eglobal) and local effect (Elocal) changes were not pronounced. Under the condition of minimum network sparsity (Dmin = 0.13), the numbers of nodes in the "right intraorbital superior frontal gyrus" (Anatomical Automatic Labeling, AAL26), right globus pallidus (AAL76), and bilateral temporal transverse gyrus (AAL79,80) in brain concussion patients were significantly lower. The numbers of nodes in the left subcapital lobe (AAL61) and left occipital gyrus (AAL51) were significantly higher, and the normalized cluster coefficients of the right intraorbital supraphalus (AAL26) and left posterior cingulate gyrus (AAL35) were significantly increased. The normalized clustering coefficients of the right triangular subfrontal gyrus (AAL55) (based on the normalized clustering coefficients of nodes in AAL14) and left sub-parietal lobes (AAL61) were significantly reduced. The mean local effects of nodes in the right intraorbital upper frontal gyrus (AAL26), left posterior cingulate gyrus (AAL35), and bilateral auxiliary motor cortex (AAL19, 20) were enhanced, whereas the mean local effects of the bilateral triangular inferior frontal gyrus (AAL13,14) and left insular cap (AAL11) were reduced (p < 0.05). CONCLUSIONS: The overall trend of network topology abnormalities in patients was random, and generalized and local functional abnormalities were seen. Changes in the function and affective circuitry of the resting default network were particularly pronounced in these patients, which we speculate may be one of the main drivers of the cognitive dysfunction and mood changes seen in concussion patients.

Disrupted topological organization of functional brain networks in traumatic axonal injury.

Traumatic axonal injury (TAI) may result in the disruption of brain functional networks and is strongly associated with cognitive impairment. However, the neural mechanisms affecting the neurocognitive function after TAI remain to be elucidated. We collected the resting-state functional magnetic resonance imaging data from 28 patients with TAI and 28 matched healthy controls. An automated anatomical labeling atlas was used to construct a functional brain connectome. We utilized a graph theoretical approach to investigate the alterations in global and regional network topologies, and network-based statistics analysis was utilized to localize the connected networks more precisely. The current study revealed that patients with TAI and healthy controls both showed a typical small-world topology of the functional brain networks. However, patients with TAI exhibited a significantly lower local efficiency compared to healthy controls, whereas no significant difference emerged in other small-world properties (Cp, Lp, γ, λ, and σ) and global efficiency. Moreover, patients with TAI exhibited aberrant nodal centralities in some regions, including the frontal lobes, parietal lobes, caudate nucleus, and cerebellum bilaterally, and right olfactory cortex. The network-based statistics results showed alterations in the long-distance functional connections in the subnetwork in patients with TAI, involving these brain regions with significantly altered nodal centralities. These alterations suggest that brain networks of individuals with TAI present aberrant topological attributes that are associated with cognitive impairment, which could be potential biomarkers for predicting cognitive dysfunction and help understanding the neuropathological mechanisms in patients with TAI.

Differential diagnosis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma based on spatial and channel attention mechanisms.

BACKGROUND: The pre-operative non-invasive differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) mainly depends on imaging. However, the accuracy of conventional imaging and radiomics methods in differentiating between the two carcinomas is unsatisfactory. In this study, we aimed to establish a novel deep learning model based on computed tomography (CT) images to provide an effective and non-invasive pre-operative differential diagnosis method for HCC and ICC. MATERIALS AND METHODS: We retrospectively investigated the CT images of 395 HCC patients and 99 ICC patients who were diagnosed based on pathological analysis. To differentiate between HCC and ICC we developed a deep learning model called CSAM-Net based on channel and spatial attention mechanisms. We compared the proposed CSAM-Net with conventional radiomic models such as conventional logistic regression, least absolute shrinkage and selection operator regression, support vector machine, and random forest models. RESULTS: With respect to differentiating between HCC and ICC, the CSAM-Net model showed area under the receiver operating characteristic curve (AUC) values of 0.987 (accuracy = 0.939), 0.969 (accuracy = 0.914), and 0.959 (accuracy = 0.912) for the training, validation, and test sets, respectively, which were significantly higher than those of the conventional radiomics models (0.736-0.913 [accuracy = 0.735-0.912], 0.602-0.828 [accuracy = 0.647-0.818], and 0.638-0.845 [accuracy = 0.618-0.849], respectively. The decision curve analysis showed a high net benefit of the CSAM-Net model, which suggests potential efficacy in differentiating between HCC and ICC in the diagnosis of liver cancers. CONCLUSIONS: The proposed CSAM-Net model based on channel and spatial attention mechanisms provides an effective and non-invasive tool for the differential diagnosis of HCC and ICC on CT images, and has potential applications in diagnosis of liver cancers.

Frequency-Dependent Alterations in the Amplitude of Low-Frequency Fluctuations in Patients with Acute Pericoronitis: A Resting-State fMRI Study.

Background: Acute pericoronitis (AP) is a common cause of odontogenic toothache. Pain significantly affects the structure and function of the brain, but alterations in spontaneous brain activity in patients with AP are unclear. Purpose: To apply the amplitude of low-frequency fluctuations (ALFF) method in resting-state functional magnetic resonance imaging to investigate altered spontaneous brain activity characteristics in patients with AP in different frequency bands (typical, slow-4, and slow-5 bands) and assess their correlation with clinical scores. Patients and Methods: Thirty-four right-handed patients with AP and 31 healthy controls (HC), matched for age, sex, education, and right-handedness, were enrolled. All subjects underwent resting-state functional magnetic resonance imaging. DPABI software was used for data preprocessing and extracting the ALFF values in different frequency bands. Subsequently, differences in ALFF values in the three bands were compared between the two groups. Correlation between ALFF values in the differential brain regions and clinical scores was assessed. Results: In the typical band, ALFF values were higher in the left insula, left superior occipital gyrus, left inferior parietal lobule, left posterior cerebellar lobule, and right postcentral gyrus in the AP than in the HC group. In the slow-4 band, ALFF values in the left superior occipital gyrus, right superior occipital gyrus, and right middle occipital gyrus were higher, and those in the right cingulate gyrus and right superior temporal gyrus were lower in the AP than in the HC group. In the slow-5 band, the ALFF values in the left insula and left superior occipital gyrus were higher in the AP than in the HC group. The ALFF values of the typical bands in the left insula, left inferior parietal lobule, and right postcentral gyrus correlated negatively, those of the slow-4 band in the right middle occipital gyrus correlated positively, and those of the slow-5 band in the left insula correlated negatively with the visual analogue scale score in the AP group. Conclusion: Our results suggested that the intrinsic brain activity of AP patients was abnormal and frequency-dependent. This provides new insights to explore the neurophysiological mechanisms of AP.

KLF14/miR-1283/TFAP2C axis inhibits HER2-positive breast cancer progression via declining tumor cell proliferation.

MiR-1283 has been identified as a tumor suppressor in some malignancies. Whereas, the role of miR-1283 in HER2-positive (HER2+) breast cancer, particularly its role in regulating cell proliferation, one of the most significant features of tumor progression, is unclear. The related microRNA screened by the breast cancer sample GSE131599 dataset were detected in HER2+ breast cancer tissues and cell lines. Then, the obtained miR-1283 was overexpressed in SKBR3 and BT-474 cells followed by relevant functional assays concerning cell proliferation and apoptosis. The xenograft mouse model was induced and the effect of miR-1283 on tumor growth and cell proliferation was examined. The target of miR-1283 and the transcription factor regulating miR-1283 were predicted and identified. Finally, the influence of transcription factor KLF14 on cell proliferation and apoptosis was investigated. An integrated analysis confirmed that miR-1283 expression was significantly decreased in HER2+ breast cancer tissues. Also, by q-RT-PCR detection, miR-1283 expression was markedly reduced in HER2+ breast cancer tissues and cell lines. The miR-1283 overexpression prevented the proliferation and enhanced apoptosis of HER2+ breast cancer cells, as well as inhibited tumor growth. Mechanistically, miR-1283 inhibited TFAP2C expression by targeting the 3'-untranslated regions of TFAP2C messenger RNA, and the KLF14 enhanced miR-1283 level via binding to its promoter. The result subsequently confirmed the KLF14/miR-1283 signaling suppressed cell proliferation in HER2+ breast cancer. Our results suggested that the KLF14/miR-1283/TFAP2C axis inhibited HER2+ breast cancer progression, which might provide novel insight into mechanical exploration for this disease.

Dynamic local metrics changes in patients with toothache: A resting-state functional magnetic resonance imaging study.

Objective: To study the dynamic changes of local metrics in patients with toothache (TA, Toothache) in the resting state, in order to further understand the changes of central neural mechanism in patients with dental pain and its effect on cognition and emotion. Methods: Thirty patients with TA and thirty matched healthy (HC) control volunteers were recruited, and resting-state functional magnetic resonance (rs-MRI) scans were performed on all subjects, and data were analyzed to compare group differences in three dynamic local indices: dynamic regional homogeneity (dReHO), dynamic low-frequency fluctuation amplitude (dALFF) and dynamic fractional low-frequency fluctuation amplitude (dfALFF). In addition, the association between dynamic local metrics in different brain regions of TA patients and scores on the Visual Analog Scale (VAS) and the Hospital Anxiety and Depression Scale (HADS) was investigated by Pearson correlation analysis. Results: In this study, we found that The local metrics of TA patients changed with time Compared with the HC group, TA patients showed increased dReHo values in the left superior temporal gyrus, middle frontal gyrus, precentral gyrus, precuneus, angular gyrus, right superior frontal gyrus, middle temporal gyrus, postcentral gyrus and middle frontal gyrus, increased dALFF values in the right superior frontal gyrus, and increased dfALFF values in the right middle temporal gyrus, middle frontal gyrus and right superior occipital gyrus (p < 0.01, cluster level P < 0.05). Pearson correlation analysis showed that dReHo values of left precuneus and left angular gyrus were positively correlated with VAS scores in TA group. dReHo value of right posterior central gyrus was positively correlated with HADS score (P < 0.05). Conclusion: There are differences in the patterns of neural activity changes in resting-state brain areas of TA patients, and the brain areas that undergo abnormal changes are mainly pain processing brain areas, emotion processing brain areas and pain cognitive modulation brain areas, which help to reveal their underlying neuropathological mechanisms. In the hope of further understanding its effects on cognition and emotion.

Circular RNA circ-ERBB2 promotes HER2-positive breast cancer progression and metastasis via sponging miR-136-5p and miR-198.

BACKGROUND: Circular RNAs (circRNAs) are pivotal regulators of various human cancers and circ-ERBB2 is abnormally expressed in breast cancer cells. However, the role and mechanism of circ-ERBB2 in HER2-positive breast cancer are still unknown. METHODS: The circ-ERBB2 expressions in the tumor tissues of HER2-positive breast cancer patients were tested using quantitative real-time PCR. The circ-ERBB2 function was investigated by cell counting kit 8 assay, Transwell, flow cytometry and Western blot. Mechanistically, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter gene assays were conducted to confirm the interaction between circ-ERBB2 and miR-136-5p or miR-198 in HER2-positive breast cancer cells. RESULTS: Circ-ERBB2 was elevated in the tumor tissues of HER2-positive breast cancer patients. Functionally, the interference with circ-ERBB2 repressed HER2-positive breast cancer cell proliferation, migration, invasion and accelerated cell apoptosis. Furthermore, the mechanistic analysis corroborated that circ-ERBB2 acted as a competing endogenous RNA for miR-136-5p or miR-198 to relieve the repressive influence of miR-136-5p or miR-198 on its target transcription factor activator protein 2C (TFAP2C). Meanwhile, in vivo assays further corroborated the oncogenic function of circ-ERBB2 in HER2-positive breast cancer. CONCLUSIONS: Circ-ERBB2 accelerated HER2-positive breast cancer progression through the circ-ERBB2/miR-136-5p/TFAP2C axis or the circ-ERBB2/miR-198/TFAP2C axis.

Functional Connectivity Density with Frequency-Dependent Changes in Patients with Diffuse Axonal Injury: A Resting-State Functional Magnetic Resonance Imaging Study.

PURPOSE: We explored changes in spontaneous brain connectivity in patients with diffuse axonal injury (DAI), assessed via functional connectivity density (FCD) tests using different frequency bands. PATIENTS AND METHODS: In all, 23 patients with DAI (17 males and 6 females) and 23 healthy controls (HCs; 17 males and 6 females) were included. Functional magnetic resonance imaging scans were performed when the participants were in a resting state and the FCD levels in three frequency bands (slow-4: 0.027-0.073 Hz, slow-5: 0.01-0.027 Hz, and typical: 0.01-0.08 Hz) were measured. In addition, Pearson's correlation coefficient was used to explore the relationship between clinical indices and brain regions with abnormal FCD values. RESULTS: Compared to HCs, DAI patients had significantly greater FCD values in the right extranuclear/limbic lobe/cingulate gyrus and left limbic lobe/hippocampus/parahippocampal gyrus, and significantly lower FCD values in the left precuneus/posterior cingulate gyrus, in the slow-4 band. In the slow-5 band, the DAI patients had higher FCD values in the left inferior temporal gyrus/superior temporal gyrus, left parahippocampal gyrus/limbic lobe, left extranuclear/cingulate gyrus, and right medial frontal gyrus, and lower values in the right inferior frontal gyrus, right inferior parietal lobule, and left cingulate gyrus/limbic lobe. Moreover, compared to HCs, the values in the typical band were higher in the right extranuclear/limbic lobe/hippocampus/parahippocampal gyrus, but were significantly lower in the right precuneus/posterior cingulate gyrus and right inferior parietal lobule/supramarginal gyrus. The abnormal FCD values of these brain regions were linearly correlated with different clinical scale scores. CONCLUSION: DAI patients had abnormal FCD values in various brain regions, indicating disruption to the brain functional network. Moreover, the values were frequency dependent. Our results provide new evidence for the pathogenesis of functional impairment and may explain the neuropathological or compensatory mechanism of the disease.

Typical radiological progression and clinical features of patients with coronavirus disease 2019.

We aimed to describe typical radiological features and progression of Coronavirus disease 2019 (COVID-19) patients. We reviewed the chest CT scans, laboratory findings, and clinical records of 66 COVID-19 patients who were admitted to affiliated hospitals of Nanchang university, Nanchang, China, from Jan 21 to Feb 2, 2020. CT was used to evaluate the radiological characteristics of COVID-19 patients. Only 4 patients (4/66, 6%) claimed their exposure to COVID-19 pneumonia patients. The major symptoms were fever (60/66, 91%) and cough (37/66, 56%). The predominant features of lesion were scattered (43/66, 65%), bilateral (50/66, 76%), ground-glass opacity (64/66, 97%), and air bronchogram sign (47/66, 71%). Forty-eight patients (48/66, 73%) had more than two lobes involved. Right lower lobe (58/66, 88%) and left lower lobe (49/66, 74%) were most likely invaded. Twelve patients (12/66, 18%) had at least one comorbid condition. Pleural traction (29/66, 44%), crazy paving (15/66, 23%), interlobular septal thickening (11/66, 17%), and consolidation (7/66, 11%) were also observed. The typical radiology features of COVID-19 patients are scattered ground-glass opacity in the bilateral lobes. Fever and cough are the major symptoms. Evaluating chest CT, clinical symptoms, and laboratory results could facilitate the early diagnosis of COVID-19, and judge disease progression.

Effects of amiloride on potassium and calcium currents in guinea pig ventricular myocytes.

AIM: To elucidate the possible mechanisms underlying antiarrhythmia of the non-selective Na+/H+ exchanger inhibitor--amiloride. METHODS: Single ventricular cells were isolated using a double-enzyme method. Effects of amiloride on voltage-dependent potassium and calcium currents in isolated guinea pig ventricular myocyte were recorded by using whole-cell patch clamp techniques. RESULTS: Exposure to amiloride (10 -100 micromol x L(-1)), the L-type and T-type calcium currents were depressed. Amiloride resulted in a concentration-dependent inhibition of peak (Ca,L), But amiloride did not change the shape of their I - V curves. It only decreased the amplitudes of the currents of the two types. When myocytes were incubated with 100 micromol x L(-1) amiloride, I(Kr) was slightly depressed and I(Ks) did not change. Amiloride (1 - 100 micromol x L(-10) depressed I(K1) in a concentration-dependent manner. CONCLUSION: Amiloride depressed potassium and calcium currents, which may give support to its uses in some diseases of the cardiovascular system.

Perforated patch recording of L-type calcium current with beta-escin in guinea pig ventricular myocytes.

AIM: To establish a perforated patch recording (PPR) mode with beta-escin and compare L-type calcium current (I(Ca,L)) recorded under PPR and normal whole-cell recording (WCR) condition in isolated guinea-pig ventricular myocytes. METHODS: Single myocytes were dissociated by enzymatic dissociation method. beta-escin was added to the pipette solution to perforate the cell membrane and obtain PPR mode. I(Ca,L) was recorded using PPR and WCR techniques. RESULTS: beta-Escin 20, 25, and 30 micromol/L could permeabilize the cell membrane and obtain PPR mode. With beta-escin 25 micromol/L, the success rate was highest (16/17, 94 %) and the time required for permibilization was 2-15 (8+/-4) min. Run-down of I(Ca,L) was considerably slower in PPR than in WCR condition. The amplitude of I(Ca,L) was decreased by 36 % at 20 min after the formation of WCR, while it was slowly decreased by 8 % at 30 min after the formation of PPR. The current-voltage relation (I-V) curves, activation and inactivation curves of I(Ca,L) were not significantly different between WCR and PPR. The inactivation rate of ICa,L was slower in PPR than in WCR, the faster inactivation time constant (tau(f)) was longer in PPR than in WCR at membrane potentials of -20 mV -- +10 mV (n=6, P<0.05), and the slower time constant (tau(s)) was also longer in PPR than in WCR at membrane potentials of -10 mV to +10 mV (n=6, P<0.05). There was no significant difference between the activation rate in WCR and PPR. CONCLUSION: Using beta-escin 25 micromol/L can easily obtain stable PPR in isolated guinea-pig ventricular myocytes, and this method is useful in dealing with channels, which show run-down under normal WCR such as L-type Ca channel.

Effects of anthopleurin-Q on myocardial hypertrophy in rats and physiologic properties of isolated atria in guinea pigs.

AIM: To study effects of anthopleurin-Q (AP-Q) on myocardial hypertrophy in rats and isolated atria in guinea pigs. METHODS: Two myocardial hypertrophy models in rats were established, one introduced by levothyroxine, the other by stenosis of abdominal aorta. Cardiac myocytes morphometry and functional experiments were employed to investigate effects of AP-Q. RESULTS: Low dose of AP-Q (1 microg/kg/d, ip) reduced morphologic changes of myocardial hypertrophy in both rat models. While high dose of AP-Q (10 microg/kg/d, ip) did not, and caused mild hydropic degeneration in cardiomyocytes. High concentration of AP-Q (30 nmol/L) enhanced the contractility, raised automaticity, and prolonged the functional refractory period (FRP) in isolated left atria of guinea pigs; higher concentration (100 nmol/L) triggered arrhythmia in right atria; low concentration of AP-Q (1 nmol/L)did not affect any myocardial properties above. CONCLUSION: Low dose of AP-Q without inotropic effect can hinder the experimental myocardial hypertrophy in rats; high dose with positive inotropic effect may be responsible for its toxic reaction.

Effects of benzyltetrahydropalmatine on potassium currents in guinea pig and rat ventricular myocytes.

AIM: To investigate the effects of benzyltetrahydropalmatine (BTHP) on rapidly activating component (I(Kr)), slowly activating component (I(Ks)) of delayed rectifier potassium current, inward rectifier potassium current (I(K1)), and transient outward potassium current (I(to)) in single ventricular myocytes. METHODS: Whole-cell patch clamp technique was used to record ionic currents. RESULTS: (1) BTHP 30 micromol/L reduced I(Kr) and I(Kr,tail) by 31 %+/-4 % and 36 %+/-5 % (n=6, P <0.01), respectively and inhibited I(Ks) and I(Ks,tail) by 40 %+/-6 % and 45 %+/-5 % (n=7, P <0.01), respectively. I(Kr) and I(Ks) were blocked by BTHP 1-100 micromol/L in a concentration-dependent fashion (IC50 value was 13.5 micromol/L and 95 % confidence limit: 11.2-15.8 micromol/L for I(Kr), 9.3 micromol/L and 95 % confidence limit: 7.8-11.8 micromol/L for I(Ks), respectively). (2) BTHP 5 micromol/L inhibited I(to) by 63 %+/-6 % (n=6, P <0.01). BTHP 1-100 micromol/L reduced I(to) in a concentration-dependent manner (IC50 value was 3.6 micromol/L and 95 % confidence limit: 2.9-4.3 micromol/L). (3) BTHP 200 micromol/L did not affect I(K1). CONCLUSION: BTHP inhibited I(Kr), I(Ks), and I(to), but not I(K1). The antiarrhythmic effects of BTHP may be mainly due to its blockade on potassium channels.

Effects of benzyltetrahydropalmatine on the rapidly activating component of delayed rectifier potassium current in guinea pig ventricular myocytes.

AIM: To investigate the effect of benzyltetrahydropalmatine (BTHP) on the rapidly activating component of delayed rectifier K+ current (Ikr) in single guinea pig ventricular myocytes. METHODS: Whole-cell patch clamp technique was used to record Ikr. RESULTS: Ikr was blocked by 1-100 mumol.L-1 BTHP in concentration-, voltage-, and specifically frequency-dependent fashion, with IC50 of 13.5 mumol.L-1 (95% confidence range: 11.2-15.8 mumol.L-1). 30 mumol.L-1 BTHP reduced Ikr and Ikr.tail by (31 +/- 4)% and (36 +/- 5)% (n = 6, P < 0.01), respectively. The time constant for deactivation (tau') of the tail current was decreased by 30 mumol.L-1 BTHP from (238 +/- 16) ms to (196 +/- 14) ms, while drug had no any effect on the time constant for activation (tau) of Ikr,tail. CONCLUSION: BTHP inhibited Ikr in a frequency-dependent fashion.

Effects of arecoline on calcium channel currents and caffeine-induced calcium release in isolated single ventricular myocyte of guinea pig.

The effects of Arecoline (Are) on calcium mobilization were investigated. In isolated single ventricular myocyte of guinea pig, patch clamp whole cell recording techniques were used to record the current of L-type calcium channel and cytosolic Ca2+ level ([Ca2+]i) labeled with fluorescence probe Fluo-3/AM was measured under a laser scanning confocal microscope. Results revealed that Are (3-100 mumol/L) could inhibit L-type calcium current in a concentration-dependent manner and the value of IC50 was 33.73 mumol/L (n = 5). In the absence of extracellular calcium, the resting levels of [Ca2+]i was not affected by Are (n = 6, P > 0.05), but pretreatment with Are (30 mumol/L) could significantly inhibit the [Ca2+]i elevation induced by caffeine (10 mmol/L, n = 6, P < 0.01). It was concluded that Are could inhibit not only calcium influx through L-type calcium channel but also calcium release from sarcoplasmic reticulum.

Effects of benzyltetrahydropalmatine on two components of the delayed rectifier K+ current in Guinea pig ventricular myocytes.

The effects of benzyltetrahydropalmatine (BTHP), a new class III antiarrhythmic agent, on the action potential in guinea pig papillary muscle and the rapidly activating component (I(Kr)) and the slowly activating component (I(Ks)) of the delayed rectifier potassium current (I(K)) in isolated guinea pig ventricular myocytes were investigated. The action potentials of papillary muscles were studied using a standard microelectrode technique, while the K(+) currents were recorded using the whole-cell patch clamp technique. The results showed that BTHP prolonged the action potential duration (APD) without altering other variables of the action potential in guinea pig papillary muscles. The 2 components of I(K) were blocked by BTHP (1 approximately 100 micromol x L(-1)) in time-, concentration-, voltage-, and specifically frequency-dependent fashion. The IC(50) value for blockade of I(Kr) was 13.5 micromol x L(-1), while the IC(50) value for blockade of I(Ks) was 9.3 micromol x L(-1). BTHP 30.0 micromol x L(-1) reduced I(Kr) and I(Kr,tail) by 31 +/- 4.3% and 36 +/- 4.7% (n = 6, p < 0.01) and decreased I(Ks) and I(Ks,tail) by 40 +/- 6.3% and 39 +/- 4.6% (n = 7, p < 0.01) respectively. BTHP accelerated their deactivation course by reducing the time constants of deactivation of I(Kr) and I(Ks). The activation kinetics of I(Kr) or I(Ks) were not affected by BTHP. It is concluded that BTHP prolonged the action potential duration with respect to its non-selective action on I(Kr) and I(Ks) in single guinea pig ventricular cell in a frequency-dependent fashion.