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Background: Mesenchymal stem cells (MSCs) are under consideration for myocardial ischemia-reperfusion (I/R) injury therapy, but their mechanism remains to be evaluated. In this article, we aimed to study the effects of the miR-29a/follistatin-like 1 axis in bone marrow-derived mesenchymal stem cells on modulating myocyte apoptosis after hypoxia-reoxygenation (H/R) injury., Methods: An in vitro myocardial ischemia-reperfusion injury model of H9c2 cells was developed by hypoxia-reoxygenation injury. The mRNA levels of follistatin-like 1, Bcl-2, Bax, and miR-29a and the protein levels of Bcl-2, Bax, cleaved caspase-3, and components of the JAK2/STAT3 pathway were detected by qRT-PCR and western blotting, respectively. Secretion of follistatin-like 1 was evaluated by enzyme-linked immunosorbent assay. Cell apoptosis was evaluated by flow cytometry. The interaction between miR-29a and follistatin-like 1 was evaluated by dual luciferase reporter assay., Results: MiR-29a suppressed the expression and secretion of follistatin-like 1 in bone marrow-derived mesenchymal stem cells. Overexpression of follistatin-like 1 in bone marrow-derived mesenchymal stem cells decreased apoptosis of myocytes induced by hypoxia-reoxygenation. Cell apoptosis in myocytes was promoted by conditioned medium from bone marrow-derived mesenchymal stem cells with ectopic miR-29a expression. Conditioned medium of miR-29a-overexpressing bone marrow-derived mesenchymal stem cells inhibited the JAK2/STAT3 pathway in myocytes to promote apoptosis of myocytes., Conclusions: MiR-29a in bone marrow-derived mesenchymal stem cells inhibits follistatin-like 1 secretion and promotes myocyte apoptosis by suppressing the JAK2/STAT3 pathway in hypoxia-reoxygenation injury., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To test the proof-of-principle that genetically-engineered mesenchymal stem cells (MSCs) transfected with the human hyperpolarization-activated cyclic nucleotide-gated channel 1 (hHCN1) gene can be modified to become cardiac pacemaker cells., Methods: MSCs were transfected with the hHCN1 gene using lentiviral-based transfection. The expressed pacemaker current (I(f)) in hHCN1-transfected MSCs was recorded using whole-cell patch-clamp analysis. The effect of the hHCN1-transfected MSCs on cardiomyocyte excitability was determined by coculturing the MSCs with neonatal rabbit ventricular myocytes (NRVM). The spontaneous action potentials of the NRVM were recorded by whole-cell current-clamp analysis., Results: A high level time- and voltage-dependent inward hyperpolarization current that was inhibited by 4 mM caesium chloride was detected in hHCN1-transfected MSCs, suggesting that the HCN1 proteins acted as I(f) channels in MSCs. The mean ± SE beating frequency in NRVMs cocultured with control MSCs transfected with the pcDNA3 plasmid control was 82 ± 8 beats/min (n = 5) compared with 129 ± 11 beats/min (n = 5) in NRVMs cocultured with hHCN1-transfected MSCs., Conclusions: Genetically-engineered MSCs transfected with the hHCN1 gene can be modified to become cardiac pacemaker cells.

Objective: The aim of this study was to study the regulatory functions of docosahexaenoic acid (DHA) on resting potential (RP), action potential duration (APD), delayed rectifier potassium current (Ik), and inwardly rectifier potassium current (Ik1) in rat ventricular myocytes, and analyze the related anti-arrhythmia mechanism., Materials and Methods: Rat ventricular myocytes were isolated by enzyme digestion method. RP, APD, Ik and Ik1 in individual ventricular myocytes were recorded by patch-clamp technique with whole-cell configuration. Effects of DHA with various concentrations (0, 20, 40, 60, 80, 100 and 120 mmol/L, respectively) on RP, AP, Ik and Ik1 were investigated., Results: There was no statistical difference of RP with different DHA concentrations (p > 0.05, n = 20), and the 25%, 50% and 90% of APD (APD25, APD50, and APD90) were gradually prolonged with increase of DHA concentration, respectively (p < 0.05, n = 20). IK gradually blocked and the I-V curve was downward shifted, according to increase of DHA concentration (p < 0.05, n = 20). The DHA half effect concentration (EC50) was 47.52 ± 2.32 µmol/L. With increasing DHA concentration, the steady-state inactivation curve shifted to left, and the recovery curve shifted to right. DHA had no significant effect on IK1 (p > 0.05, n = 20)., Conclusions: DHA has regulatory functions on RP, APD, Ik and Ik1 in rat ventricular myocytes, which may be one of the related antiarrhythmic mechanisms.

Objective: To investigate the effects of docosahexaenoic acid (DHA) on sodium channel current (I(Na)) and transient outward potassium channel current (I(to)) in rat ventricular myocytes and to evaluate potential anti-arrhythmic mechanisms of DHA., Methods: I(Na) and I(to) of individual ventricular myocytes were recorded by patch-clamp technique in whole-cell configuration at room temperature. Effects of DHA at various concentrations (0, 20, 40, 60, 80, 100 and 120 micromol/L) on I(Na) and I(to) were observed., Results: (1) I(Na) was blocked in a concentration-dependent manner by DHA, stably inactivated curves were shifted to the left, and recover time from inactivation was prolonged while stably activated curves were not affected by DHA. At -30 mV, I(Na) was blocked to (1.51 ± 1.32)%, (21.13 ± 4.62)%, (51.61 ± 5.73)%, (67.62 ± 6.52)%, (73.49 ± 7.59)% and (79.95 ± 7.62)% in the presence of above DHA concentrations (all P < 0.05, n = 20), and half-effect concentration (EC(50)) of DHA on I(Na) was (47.91 ± 1.57)micromol/L. (2) I(to) were also blocked in a concentration-dependent manner by DHA, stably inactivated curves were shifted to the left, and recover time from inactivation was prolonged with increasing concentrations of DHA, and stably activated curves were not affected by DHA. At +70 mV, I(to) was blocked to (2.61 ± 0.26)%, (21.79 ± 4.85)%, (63.11 ± 6.57)%, (75.52 ± 7.26)%, (81.82 ± 7.63)% and (84.33 ± 8.25)%, respectively, in the presence of above DHA concentrations (all P < 0.05, n = 20), and the EC(50) of DHA on I(to) was (49.11 ± 2.68)micromol/L., Conclusion: The blocking effects of DHA on APD and I(to) may serve as one of the anti-arrhythmia mechanisms of DHA.

The goal of this study was to determine the mechanisms of n-3 polyunsaturated fatty acids (n-3 PUFA) on anti-arrhythmias and prevention of sudden death. The calcium-tolerant Sprague-Dawley rat ventricular myocytes were isolated by enzyme digestion. Effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on action potentials and transient outward potassium currents (I (to)) of epicardial ventricular myocytes were investigated using whole-cell patch clamp techniques. Action potential durations (APDs) and I (to) were observed in different concentrations of DHA and EPA. APD(25), APD(50), and APD(90) with 0.1 μmol/L DHA and EPA were prolonged less than 15% and 10%. However, APDs were prolonged in concentration-dependent manners when DHA and EPA were more than 1 μmol/L. APD(25), APD(50), and APD(90) were 7.7 ± 2.0, 21.2 ± 3.5, and 100.1 ± 9.8 ms respectively with 10 μmol/L DHA, and 7.2 ± 2.5, 12.8 ± 4.2, and 70.5 ± 10.7 ms respectively with 10 μmol/L EPA. I (to) currents were gradually reduced with the increased concentrations of DHA and EPA from 1 to 100 μmol/L, and their half-inhibited concentrations were 2.3 ± 0.2 and 3.8 ± 0.6 μmol/L. The results showed APDs were prolonged and I (to) current densities were gradually reduced with the increased concentrations of DHA and EPA. The anti-arrhythmia mechanisms of n-3 PUFA are complex, however, the effects of n-3 PUFA on action potentials and I (to) may be one of the important mechanisms.

Background: There are many reports about the anti-arrhythmic effects of omega-3 polyunsaturated fatty acids, however, the mechanisms are still not completely delineated. The purpose of this study was to investigate the characteristics of action potentials and transient outward potassium currents (Ito) of Sprague-Dawley rat ventricular myocytes and the effects of docosahexaenoic acid (DHA) on action potentials and Ito., Methods: The calcium-tolerant rat ventricular myocytes were isolated by enzyme digestion. Action potentials and Ito of epicardial, mid-cardial and endocardial ventricular myocytes were recorded by whole-cell patch clamp technique., Results: 1. Action potential durations (APDs) were prolonged from epicardial to endocardial ventricular myocytes (P < 0.05). 2. Ito current densities were decreased from epicardial to endocardial ventricular myocytes, which were 59.50 +/- 15.99 pA/pF, 29.15 +/- 5.53 pA/pF, and 12.29 +/- 3.62 pA/pF, respectively at +70 mV test potential (P < 0.05). 3. APDs were gradually prolonged with the increase of DHA concentrations from 1 micromol/L to 100 micromol/L, however, APDs changes were not significant as DHA concentrations were in the range of 0 micromol/L to 1 micromol/L. 4. Ito currents were gradually reduced with the increase of DHA concentrations from 1 micromol/L to 100 micromol/L, and its half-inhibited concentration was 5.3 micromol/L. The results showed that there were regional differences in the distribution of action potentials and Ito in rat epicardial, mid-cardial and endocardial ventricular myocytes. APDs were prolonged and Ito current densities were gradually reduced with the increase of DHA concentrations., Conclusion: The anti-arrhythmia mechanisms of DHA are complex, however, the effects of DHA on action potentials and Ito may be one of the important causes.

Objective: To investigate the effects of docosahexaenoic acid (DHA) on action potential (AP) and transient outward potassium current (I(to)) on ventricular myocytes of Sprague-Dawley rat., Methods: Calcium-tolerant ventricular myocytes were isolated by enzyme digestion. The changes of AP and I(to) with increasing DHA at concentrations of 0, 10, 20, 40, 60, 80, 100, 120 and 200 micromol/L were recorded by whole-cell patch clamp configuration., Results: (1) Action potential durations (APDs) were not affected by DHA at concentrations from 0 micromol/L to 30 micromol/L, while APDs were gradually prolonged in proportion with increasing DHA concentrations from 30 micromol/L to 200 micromol/L within 5 minutes and remained stable thereafter. APD(25), APD(50) and APD(75) were (7.7 +/- 2.0) ms, (21.2 +/- 3.5) ms, and (100.1 +/- 9.8) ms respectively at 100 micromol/L DHA. APD(25), APD(50), and APD(75) were (15.2 +/- 4.0) ms, (45.7 +/- 6.8) ms, and (215.6 +/- 15.7) ms respectively at 200 micromol/L DHA. (2) I(to) was gradually reduced with the increasing DHA concentrations from 10 micromol/L to 200 micromol/L. I(to) was blocked by DHA in a dose-dependent manner. I(to) current density was (30.1 +/- 7.2) pA/pF at DHA concentration of 60 micromol/L and its half-inhibition concentration was 58.3 micromol/L., Conclusion: APDs are gradually prolonged while I(to) reduced with increasing concentrations of DHA which might contribute to the anti-arrhythmia mechanisms of DHA.

Aim: To record funny currents (If) of ventricular myocytes and to analysize hyperpolarization-activated cation channel(HCN) expression in the rats of different ages., Methods: Fresh ventricular myocytes were isolated from 3 days rats and adult rats.HCN expressions were measured by real-time quantitative polymerase chain reaction(real-time PCR). It was recorded through whole-cell patch clamp., Results: HCN1, HCN2, HCN3, HCN4 mRNA represented 0.23% +/- 0.01%, 83.58% +/- 0.04%, 0.79% +/- 0.01%, 15.44% +/- 0.01% of total HCN mRNA in the neonatal rats, respectively. If was recorded and the threshold for activation was -75 mV. In the adult rat, HCN1, HCN2, HCN3, HCN4 mRNA represented 0.72% +/- 0.02%, 91.58% +/- 0.08%, 0.27% +/- 0.02%, 7.12% +/- 0.02% of total HCN mRNA. The ratio of HCN2 to HCN4 was approximately (13.06 +/- 0.21):1. The threshold for activation of If was approximately -115 mV in the adult rats., Conclusion: With the development of rats, the value of If is smaller. The threshold for activation of If is more negative. The ratio of HCN2 to HCN4 is bigger.

To investigate the effects of S- and R-amlodipine (Aml) on action potential (AP) and L-type calcium channel current (ICa-L), the whole-cell patch-clamp technique was used on rat ventricular myocytes to record AP, ICa-L, peak currents, steady-state activation currents, steady-state inactivation currents, and recovery currents from inactivation with S-Aml and R-Aml at various concentrations. Increasing concentrations of S-Aml gradually shortened AP durations (APDs). At concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L, S-Aml blocked 1.5% +/- 0.2%, 25.4% +/- 5.3%, 65.2% +/- 7.3%, 78.4% +/- 8.1%, and 94.2% +/- 5.0% of ICa-L, respectively (p < 0.05), and the half-inhibited concentration was 0.62 +/- 0.12 micromol/L. Current-voltage curves were shifted upward; steady-state activation and inactivation curves were shifted to the left. At these concentrations of S-Aml, the half-activation voltages were -16.01 +/- 1.65, -17.61 +/- 1.60, -20.17 +/- 1.46, -21.87 +/- 1.69, and -24.09 +/- 1.87 mV, respectively, and the slope factors were increased (p < 0.05). The half-inactivation voltages were -27.16 +/- 4.48, -28.69 +/- 4.52, -31.19 +/- 4.17, -32.63 +/- 4.34, and -35.16 +/- 4.46 mV, respectively, and the slope factors were increased (p < 0.05). The recovery times from inactivation of S-Aml were prolonged (p < 0.05). In contrast, R-Aml had no effect on AP and ICa-L (p > 0.05) at the concentrations tested. Thus, only S-Aml has calcium channel blockade activity, whereas R-Aml has none of the pharmacologic actions associated with calcium channel blockers.

Objective: Amlodipine (Aml) has R- and S-isomers with different pharmacological effects. However, no data are available on the influence of (S)-Aml and (R)-Aml on L-type calcium channel current (I(Ca-L)) or cytosolic calcium (Ca2+). This study is to investigate effects on I(Ca-L) and cytosolic Ca2+., Methods: I(Ca-L), peak currents, I-V curves, steady state activation curves, steady state inactivation curves and recovery curves from inactivation with (S)-Aml and (R)-Aml were recorded by whole-cell patch clamp configuration. Cytosolic Ca2+ of smooth muscle cells was assayed by Fura-2/AM., Results: At the concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L, 1.5 +/- 0.2%, 25.4 +/- 5.3%, 65.2 +/- 7.3%, 78.4 +/- 8.1%, and 94.2 +/- 5.0% of I(Ca-L) were blocked by (S)-Aml. I-V curves were shifted upward. Half-activation voltages were -16.01 +/- 1.65 mV, -17.61 +/- 1.60 mV, -20.17 +/- 1.46 mV, -21.87 +/- 1.69 mV and -24.09 +/- 1.87 mV (P < 0.05). Half-inactivation voltages were -27.16 +/- 4.48 mV, -28.69 +/- 4.52 mV, -31.19 +/- 4.17 mV, -32.63 +/- 4.34 mV and -35.16 +/- 4.46 mV (P < 0.05). Recovery time were prolonged gradually (P < 0.05). 10.3 +/- 1.2%, 35.2 +/- 3.5%, 60.1 +/- 5.0%, 78.9 +/- 6.1%, and 91.2 +/- 7.6% of cytosolic Ca2+ were reduced at different concentrations (P < 0.05). However, (R)-Aml at different concentrations had no effect on I(Ca-L) and cytosolic Ca2+ (P > 0.05)., Conclusion: Only (S)-Aml has calcium channel blockade activity, while (R)-Aml has none of the pharmacologic actions associated with CCBs.

Objective: To investigate the effects of different amlodipine isomers on L-type calcium current (ICa-L) and kinetics of rat ventricular myocytes., Methods: Rat ventricular myocytes were isolated by enzyme digestion. ICa-L, peak currents, I-V curves, steady state activation curves, steady state inactivation curves and recovery curves from inactivation with S-amlodipine, R-amlodipine and R, S-amlodipine at concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L were recorded by whole-cell patch clamp configuration., Results: At the concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L, ICa-L were blocked in a dose-dependent manner by S-amlodipine [(1.5 +/- 0.2)%, (25.4 +/- 5.3)%, (65.2 +/- 7.3)%, (78.4 +/- 8.1)%, and (94.2 +/- 5.0)%] and by R, S-amlodipine [(0.9 +/- 0.1)%, (10.4 +/- 3.2)%, (69.1 +/- 5.3)%, (75.2 +/- 7.0)%, and (81.6 +/- 6.4)%]. I-V curves were significantly shifted upward, steady state activation and inactivation curves were significantly shifted to left by S-amlodipine and R, S-amlodipine (0.1 micromol/L to 10 micromol/L). Recovery time from inactivation was also significantly prolonged by S-amlodipine [(210.1 +/- 19.5) ms, (225.2 +/- 21.3) ms, (241.7 +/- 20.3) ms, (252.3 +/- 24.2) ms, and (282.6 +/- 23.2) ms] and by R, S-amlodipine [(208.7 +/- 17.4) ms, (215.8 +/- 18.3) ms, (225.2 +/- 21.3) ms, (235.8 +/- 22.7) ms, and (252.3 +/- 24.2) ms] in a dose-dependent manner. The observed effects of S-amlodipine were more potent than those of R, S-amlodipine (P < 0.05). However, all these parameters were not affected by R-amlodipine at various concentrations (P > 0.05)., Conclusion: L-type calcium current of rat ventricular myocytes could be blocked by R, S-amlodipine and S-amlodipine in a dose-dependent manner.

Objective: To analysis the effect of amiodarone on funny current (I(f)) and hyperpolarization-activated cation channel (HCN) gene expressions of the neonatal rat ventricular myocytes., Methods: Ventricular myocytes of 1 - 3 days-old rats were isolated and cultured. The cardiomyocytes were treated by amiodarone (0.01, 0.1, 1, 10, 100 micromol/L) for 3 hours or amiodaron (10 micromol/L) for 0, 0.5, 1, 3, 6 hours. The I(f) and HCN 1 - 4 gene expressions were measured through the whole-cell configuration of the patch-clamp technique and real-time quantitative polymerase chain reaction (real-time PCR) using SYBR Green PCR kit., Results: (1) HCN1, HCN2, HCN3 and HCN4 represented (0.23 +/- 0.01)%, (83.58 +/- 0.04)%, (0.79 +/- 0.01)% and (15.44 +/- 0.01)% of total HCN mRNA, respectively. (2) Amiodaron resulted in a dose-dependent I(f) [(3.1 +/- 0.9)%, (9.7 +/- 2.4)%, (36.7 +/- 5.8)%, (80.3 +/- 1.8)% and (85.9 +/- 3.1)%, respectively at -145 mV, IC(50) (1.32 +/- 0.28) micromol/L], HCN2 [(2.1 +/- 0.8)%, (8.9 +/- 3.6)%, (30.1 +/- 4.2)%, (78.3 +/- 3.6)% and (81.1 +/- 1.9)%, respectively] and HCN4 decrease [(0.5 +/- 0.2)%, (2.1 +/- 2.6)%, (8.8 +/- 3.2)%, (60.1 +/- 4.6)% and (59.6 +/- 6.5)%, respectively]. (3) Amiodaron (10 micromol/L) also induced a time-dependent I(f) [(1.1 +/- 0.1)%, (12.6 +/- 2.3)%, (80.6 +/- 2.2)% and (80.1 +/- 2.1)%, respectively], HCN2 [(1.0 +/- 0.1)%, (9.8 +/- 3.9)%, (82.9 +/- 4.6)% and (83.9 +/- 1.7)%, respectively] and HCN4 decrease [(0.1 +/- 0.1)%, (1.9 +/- 1.1)%, (59.4 +/- 7.8)% and (60.9 +/- 3.1)%, respectively]. However, HCN1 and HCN3 expressions were not affected by amiodaron treatment., Conclusion: Current density of I(f) and the expression of HCN2 and HCN4 were decreased by amiodaron which might be the possible antiarrhythmic working mechanisms of amiodaron.

Objective: To investigate the effects of metoprolol on cardiac function and myocyte calcium regulatory protein expressions in rabbits with heart failure., Methods: Rabbit heart failure model was established by aortic insufficiency induced volume overload followed 14 days later by pressure overload induced by abdominal aorta constricting (HF, n = 11), another 8 rabbits with heart failure were treated with metoprolol (ME) for 6 weeks, sham-operated rabbits (n = 11) served as control. Cardiac function was measured by echocardiography at the end of study. Caffeine-induced calcium transients of myocytes loaded by Fluo-3/AM were observed under Laser scanning confocal microscope. Calcium regulatory protein expression was determined by Western blot analysis., Results: Compared to control animals, the ejection fractions [EF, (45.7 +/- 3.0)% vs. (72. 6 +/- 5.0)%, P < 0.01] and the amplitude of caffeine-induced calcium transients [(16.0 +/- 3.5) FI vs. (43.5 +/- 6.2) FI, P < 0.01] were significantly decreased while its time to peak was significantly prolonged [(129.8 +/- 14.5) s vs. (52.2 +/- 7.4) s, P < 0.01] in HF rabbits. The RyR2 (0.106 +/- 0.007 vs. 0.203 +/- 0.021, P < 0.01) and the ratio of SERCA2a and NCX (1.22 +/- 0.23 vs. 1.96 +/- 0.12, P < 0.01) were also significantly reduced in myocytes of HF rabbits. Metoprolol significantly attenuated the decrease of EF [(60.2 +/- 5.1)%], the amplitude of calcium transient [(32.8 +/- 5.4) FI], the RyR2 expression (0.164 +/- 0.016) and the ratio of SERCA2a and NCX (1.68 +/- 0.17, all P < 0.05 vs. HF rabbits) and attenuated the increase of the time to peak of caffeine-induced calcium transients [(91.4 +/- 10.9) s, P < 0.05 vs. HF rabbits]., Conclusion: Metoprolol could improve the cardiac function possibly by preventing the alterations of calcium regulatory proteins and increasing calcium transients in failing heart.

Pacemaker cells differ from common cardiomyocytes for the presence of a spontaneous depolarization process during the diastolic phase of the cardiac cycle, which is due to the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel genes, providing the presence of an inward current. With this in mind, we embarked on a study to test proof-of-principle if genetically engineered mesenchymal stem cells (MSCs) transfected with HCN2 genes can be modified to be cardiac pacemaker cells. In addition to expressing an anticipated high level of hHCN2 gene, MSCs transfected with HCN2 genes by LentiV in our study also expressed characteristic hHCN2 protein, the I(f)-like current and were capable of increasing the spontaneous beating rate of cocultured cardiac myocytes. Control MSCs did not exert these effects. Thus, the electrical effects of the MSCs transfected with the hHCN2 gene were similar to the effects of overexpression of the same gene in the myocytes in vitro system. For stable genetic modification, we used the self-inactivating HIV1-based lentiviral vector (LentiV) for transgene delivery in our study, which can integrate transgene into the host genome. This unique property makes LentiV ideal for modifying MSCs, which allows persistent transgene expression. With these findings, we hypothesize that genetically engineered MSCs transfected with HCN2 genes by LentiV can be modified to be cardiac pacemaker cells.

Objective: The aim of the present study was to investigate the acute action of amiodarone (AM) on the inward currents I(Na), I(Ca-L) and outward currents I(k), I(k1), I(to) in hypertrophied and normal rat ventricular myocytes., Methods: The pressure overload hypertrophy rat model was established by partial ligation of ascending aorta for 4 weeks. Ventricular myocytes were exposed to 0.01, 0.1, 1, 10 and 50 micromol/L AM and whole cell patch clamp technique was used to study the acute effects of AM on the inward currents I(Na), I(Ca-L) and outward currents I(k), I(k1), I(to)., Results: (1) Compared with the normal ventricular myocytes, the current density of I(k), I(ks), I(to) and I(k1) were all decreased in hypertrophied myocytes, but I(Na) and I(Ca-L) remained unchanged. (2) I(Ca-L) was blocked by 59.0% +/- 4.4% in normal myocytes but only blocked by 16.7% +/- 8.0% in hypertrophied myocytes after 50 micromol/L AM application; IC(50) of I(Na) were 9.2 micromol/L and 5.9 micromol/L in normal and in hypertrophied myocytes, respectively; I(to) was blocked by 55.9% +/- 5.5% in normal myocytes and 23.0% +/- 2.8% in hypertrophied myocytes after 50 micromol/L AM application. I(k1) was not affected by AM in both normal and hypertrophied myocytes; I(ks) was blocked by 21.6% +/- 5.6% in normal myocytes and 42.7% +/- 9.2% in hypertrophied myocytes after 10 micromol/L AM application., Conclusion: Our results show that the sensitivity of hypertrophied myocytes to AM on I(Na), I(ks) were higher than that of normal myocytes, while the sensitivity on I(Ca-L), I(k1), I(to) were lower than that of normal myocytes favoring the use of AM on hypertrophied myocardium for antiarrhythmic therapy.