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M J Su

Publications and source records attributed to M J Su.

At least 55 records · Page 3Linked to original sources
PubMed1994

Dicentrine, an alpha-adrenoceptor antagonist with sodium and potassium channel blocking activities.

To elucidate the electrophysiological effect of dicentrine, an alkaloid isolated from Lindera megaphylla, we examined action potential and membrane currents in single cardiac cells. The tight-seal whole cell clamp technique was used. In the current clamp condition, 3 microM dicentrine prolonged rat ventricular action potential duration (APD50) from 38.9 +/- (SEM)9.8 ms to 147.8 +/- 19.7 ms (n = 12) and reduced its maximal rate of depolarization (Vmax) from 220.5 +/- 20.3 V/s to 37.0 +/- 4.0 V/s. The same concentration of quinidine increased APD50 from 42.5 +/- 5.2 ms to 182.8 +/- 15.6 ms (n = 6) and decreased the Vmax from 225.4 +/- 19.5 V/s to 32.2 +/- 3.0 V/s. Voltage clamp study revealed that dicentrine (1 to 100 microM) inhibited the integral of the transient outward current (Ito-I200) dose-dependently with a KD value of 3.0 +/- 0.5 microM. At 50 mV, the suppression of Ito by 3 microM dicentrine was accompanied by shortening of its inactivation time constant from 41.0 +/- 4.9 ms to 18.8 +/- 2.1 ms. V0.5 for the steady state inactivation curve of Ito was shifted from -25.5 +/- 2.8 mV to -40.6 +/- 2.1 mV. Compared to dicentrine, quinidine exerted stronger but the same mode of inhibition of Ito. 4-Aminopyridine, however, blocked Ito without modification of its inactivation time constant. In addition to the inhibition of Ito, the late outward current (Ilo) was significantly reduced by 10 microM each of dicentrine and quinidine to 60.0 +/- 13.3% and 37.5 +/- 6.3%, respectively. 4-Aminopyridine (2 mM) failed to inhibit this current.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

The electrophysiological effects of dicentrine on the conduction system of rabbit heart.

1. The electrophysiological effects of dicentrine, an aporphine alkaloid isolated from the root of Lindera megaphylla, were examined in the Langendorff perfused rabbit heart and rabbit isolated cardiac cells. 2. Standard electrophysiological characters were measured in the Langendorff perfused rabbit heart (control study) and after 5 min exposure to 1, 3 and 9 microM of dicentrine and during the subsequent recovery phase sequentially (n = 7). The same study protocols were performed in 0.5 to 4.5 microM quinidine (n = 7), 18 to 162 microM procainamide and N-acetylprocainamide (n = 7) for comparison. 3. The results showed that the spontaneously beating heart rate and the sinoatrial (SA) and atrioventricular nodal (AH) conduction time were not significantly affected by dicentrine but were significantly suppressed by the higher doses of quinidine (4.5 microM) and procainamide (162 microM). 4. The His-Purkinje conduction time was significantly increased by the higher dose of dicentrine, quinidine and procainamide. 5. The ventricular repolarization time and its effective refractory period were significantly increased by the higher dose of dicentrine and the other agents. 6. The effective refractory period of the atrium, AV node and His-Purkinje system were also significantly increased by dicentrine and the other agents. 7. A voltage clamp study revealed that the prolongation of atrial action potential duration by dicentrine (9 microM) was associated with a significant inhibition of the transient potassium outward current. As well as inhibition of the transient outward current, a significant inhibition of the sodium inward current by dicentrine was found. 8.We conclude that (1) dicentrine is potentially a useful antiarrhythmic agent with type Ia and type III antiarrhythmic action; (2) the relative potency of dicentrine on the electrophysiological function of cardiac tissue is 10-20 times more than that of procainamide.

Action Potentials↗
PubMed1994

The electrophysiological effects of antiarrhythmic potential of a secoaporphine, N-allylsecoboldine.

1. A satisfactory antiarrhythmic potential of N-allylsecoboldine, a synthetic derivative of secoaporphine, has been documented. Its effects on the ionic currents of cardiac myocytes and the influence on the electrophysiological properties of the conduction system in Langendorff perfused hearts were investigated. 2. Ionic currents were studied by voltage clamp in the whole cell configuration. N-allylsecoboldine blocked the Na channel with a leftward-shift of its half voltage-dependent inactivation and a slower rate of recovery from the inactivation state. Similarly, calcium inward currents were inhibited but to a much smaller extent. 3. N-allylsecoboldine inhibited the 4-AP-sensitive transient outward K current. Currents through the K1 channels were also reduced. 4. As compared with quinidine, N-allylsecoboldine caused a comparable degree of block on Na and K1 currents but blocked to a lesser extent the Ca and Ito currents. 5. In the perfused whole-heart model, N-allylsecoboldine caused a dose-dependent prolongation in sinoatrial, atrioventricular and His-Purkinje system conduction intervals and prolonged the effective refractory periods of the atrium, AV node, His-Purkinje system and ventricle. However, the basic cycle length was not significantly affected. As compared to quinidine, N-allylsecoboldine exerted less pronounced effects on both the basic cycle length and the atrial and AV nodal refractory periods. 6. We conclude that N-allylsecoboldine predominantly blocks Na and K1 channels and in similar concentrations partly blocks Ca channels and Ito. These effects result in a modification of the electrophysiological properties of the conduction system which provides a satisfactory therapeutic potential for the treatment of cardiac arrhythmias.

Animals↗
PubMed1994

Pharmacological characteristics of liriodenine, isolated from Fissistigma glaucescens, a novel muscarinic receptor antagonist in guinea-pigs.

1. The pharmacological activities of liriodenine, isolated from Fissistigma glaucescens, were determined in isolated trachea, ileum and cardiac tissues of guinea-pigs. 2. Liriodenine was found to be a muscarinic receptor antagonist in guinea-pig trachea as revealed by its competitive antagonism of carbachol (pA2 = 6.22 +/- 0.08)-induced smooth muscle contraction. It was slightly more potent than methoctramine (pA2 = 5.92 +/- 0.05), but was less potent than atropine (pA2 = 8.93 +/- 0.07), pirenzepine (pA2 = 7.02 +/- 0.09) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, pA2 = 8.72 +/- 0.07). 3. Liriodenine was also a muscarinic antagonist in guinea-pig ileum (pA2 = 6.36 +/- 0.10) with a pA2 value that closely resembled that obtained in the trachea. 4. Liriodenine was 10 fold less potent in atrial preparations (left atria, pA2 = 5.24 +/- 0.04; right atria, pA2 = 5.35 +/- 0.09 and 5.28 +/- 0.07 for inotropic and chronotropic effects, respectively) than in smooth muscle preparations. 5. High concentration of liriodenine (300 microM) partially depressed the contractions induced by U-46619, histamine, prostaglandin F2 alpha, neurokinin A, leukotriene C4 and high K+ in the guinea-pig trachea. The inhibitions were characterized by a rightward shift in the concentration-response curves with suppression of their maximal contraction. 6. High concentration of liriodenine (300 microM) did not affect U-46619- or neurokinin A-induced tracheal contraction in the presence of nifedipine (1 microM) or in Ca(2+)-free (containing 0.2 mM EGTA) medium. 7. Neither cyclic AMP nor cyclic GMP content of guinea-pig trachealis was changed by liriodenine (30-300 microM). 8. It is concluded that liriodenine is a selective muscarinic receptor antagonist in isolated trachea, ileum and cardiac tissues of guinea-pigs. It is more potent in smooth muscle than in cardiac preparations. It also acts as a blocker of voltage-dependent Ca2+ channels at a high concentration (300 microM).

Animals↗
PubMed1994

Comparison of the pharmacologic action of two isoquinoline alkaloids on rat cardiac tissue.

We investigated the action of two synthetic isoquinoline alkaloids, 3,4-dihydroxybenzyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (CSH109) and 2-bromo-3,4-dimethoxybenzyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (CSH118) on rat cardiac tissue. In the right atria, CSH109 increased the amplitude of contractions and spontaneous beats dose-dependently. In the driven left atria and right ventricular strips, CSH109 caused a similar increase in contractions. The positive inotropic and chronotropic actions of CSH109 were antagonized by propranolol. CSH118 caused the spontaneous beats in the right atria to slow down. CSH118, however, failed to antagonize the positive inotropic effect and positive chronotropic effect of isoprenaline. Electrophysiologic study revealed that 3 microM CSH118 markedly reduced fast action potential upstroke and prolonged the action potential duration (APD50) of rat ventricular cells from 34 +/- 8 msec to 122 +/- 29 msec (n = 6). CSH109 prolonged APD50 slightly from 24 +/- 4 msec to 38 +/- 7 msec (n = 4). Under voltage clamp conditions, CSH109 significantly increased the L-type calcium inward current (ICa). The TTX-sensitive sodium inward current (INa), transient outward (Ito) and late outward current (I800), however, were unaffected. The increase in ICa by CSH109 was effectively antagonized by propranolol. Contrary to the action of CSH109, CSH118 strongly suppressed INa, ICa, Ito and I400. The inhibition of INa by 1.5 to 9 microM CSH118 was associated with negative shifting of its steady state inactivation curve. It is concluded that CSH109 exerts a cardiac effect by activating the B-adrenoceptor. CSH118, however, is a broad spectrum ionic channel blocker.

Action Potentials↗
PubMed1993

Vasoconstricting effect in rat aorta caused by thaliporphine isolated from the plant Neolitsea konishii K.

Thaliporphine (0.1-100 microM) produced sustained, concentration-dependent contraction in isolated rings of rat aorta. Thaliporphine (ED50 = 1.5 +/- 0.5 microM) was less potent than endothelin (ED50 = 3.9 +/- 0.4 nM), but was more potent than Bay K 8644 (ED50 = 5.5 +/- 0.6 microM). Thaliporphine also contracted guinea-pig trachea and ileum preparations, and increased the force of beating of rat left atria, but was less potent on these tissues than on rat aorta. Thaliporphine-induced contraction of rat aorta was not affected by prazosin (0.3 microM), atropine (1 microM), saralasin (10 microM) or ketanserin (10 microM). However, the contraction was slightly potentiated by the removal of endothelium. Preincubation of the rat aorta in Ca(2+)-free Krebs solution (containing 1 mM EGTA) for 15 min completely abolished thaliporphine-induced contractions, and the subsequent addition of 3 mM CaCl2 restored thaliporphine-induced contractions to the control level. In rat aorta, thaliporphine-induced contractions were significantly reduced by nifedipine (1-30 nM) or verapamil (0.01-0.3 microM), and significantly increased by Bay K 8644 (0.1 microM) or KCl (20 mM). The pA2 values for nifedipine and verapamil against thaliporphine-induced contractions were 9.4 +/- 0.1 and 8.4 +/- 0.2, respectively. The results indicate that thaliporphine exerts its vasoconstrictor effect on rat aorta mainly by promoting Ca2+ entry.

Animals↗
PubMed1993

Mechanical and electrophysiological studies on the positive inotropic effect of 2-phenyl-4-oxo-hydroquinoline in rat cardiac tissues.

1. The pharmacological and electrophysiological effect of 2-phenyl-4-oxo-hydroquinoline (YT-1), a new synthetic agent, were determined in rat isolated cardiac tissues and ventricular myocytes. 2. YT-1 was found to have a positive inotropic effect in both atria and ventricular muscles but did not cause significant increases in the spontaneously beating rate of right atria. 3. The positive inotropic effect of YT-1 was antagonized neither by beta-nor by alpha-adrenoceptor antagonists but was partially antagonized by a Ca2+ channel blocker (verapamil) and a K+ channel blocker (4-AP). 4. The action potential duration and amplitude of ventricular cells were progressively increased as the concentration of YT-1 was increased from 3 to 30 microM. 5. A voltage clamp study revealed that the prolongation of action potential duration by YT-1 was associated with a prominent inhibition of 4-AP-sensitive transient outward current (I(to)). At potentials negative to the reversal potential of K1-channels, the inward current through these channels was partially reduced by YT-1. At potentials positive to the reversal potential, the outward current through these channels was affected very little. 6. Although YT-1 blocked the amplitude of I(to), the voltage-dependence of the steady-state inactivation of I(to), was unaffected. 7. Apart from the inhibition of K+ currents, YT-1 also inhibited the sodium inward current. 8. The evidence suggests that YT-1 increases the slow inward Ca2+ current (ICa) significantly. 9. It is concluded that the positive inotropic effect of YT-1 is due predominantly to the increase of ICa and inhibition of I(to).

Action Potentials↗
PubMed1993

Pharmacological activity of (-)-discretamine, a novel vascular alpha-adrenoceptor and 5-hydroxytryptamine receptor antagonist, isolated from Fissistigma glaucescens.

1. The pharmacological activity of (-)-discretamine, isolated from Fissistigma glaucescens, was determined in rat isolated thoracic aorta, cardiac tissues and ventricular myocytes and guinea-pig isolated trachea. 2. (-)-Discretamine was found to be an alpha 1-adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of noradrenaline (pA2 = 7.20 +/- 0.10)- or phenylephrine (pA2 = 7.60 +/- 0.09)-induced vasoconstriction. It was as potent as phentolamine (pA2 = 7.51 +/- 0.10), but was more potent than yohimbine (pA2 = 6.18 +/- 0.06). Removal of endothelium significantly increased the antagonistic potency of (-)-discretamine on noradrenaline (pA2 = 7.52 +/- 0.09)- or phenylephrine (pA2 = 7.90 +/- 0.09)-induced vasoconstriction. 3. (-)-Discretamine was also an alpha 2-adrenoceptor blocking agent (pA2 = 6.30 +/- 0.15) and a 5-hydroxytryptamine antagonist (pA2 = 6.87 +/- 0.06), both in rat aorta denuded of endothelium. 4. (-)-Discretamine protected alpha-adrenoceptors from alkylation by the irreversible blocking agent, phenoxybenzamine. 5. [3H]-inositol monophosphate formation caused by noradrenaline (3 microM) in rat thoracic aorta was suppressed by (-)-discretamine (10 and 30 microM) and prazosin (3 microM). 6. A high concentration of (-)-discretamine (30 microM) did not affect the contraction induced by the thromboxane receptor agonist U-46619, prostaglandin F2 alpha (PGF2 alpha), angiotensin II, high K+ or endothelin in rat aorta denuded of endothelium. Neither cyclic AMP nor cyclic GMP content of rat thoracic aorta was changed by (-)-discretamine. 7. Contraction of guinea-pig trachea caused by histamine, leukotriene C4 or carbachol was not affected by (-)-discretamine (30 microM). (-)-Discretamine also did not block beta l- or beta2-adrenoceptor-mediated responses induced by isoprenaline in rat right atria and guinea-pig trachea.8. A voltage clamp study in rat ventricular single myocytes revealed that sodium inward current, slow inward Ca2+ current or transient (ItO) and steady state (I800) outward current was not affected by(-)-discretamine (30 microM).9. It is concluded that (-)-discretamine is a selective x-adrenoceptor and 5-HT receptor antagonist in vascular smooth muscle.

Adrenergic alpha-Antagonists↗
PubMed1993

Comparison of the electrophysiological effects of S49, CSH087 and CSH068 in rat ventricular cells.

S49, CSH087 and CSH068 are aporphine alkaloids and are synthesized from vanillin. In the present study, the effects of these compounds on the action potential and membrane currents of rat ventricular cells were examined by using the whole cell recording technique with single suction pipettes. At a stimulation frequency of 0.1 Hz, S49 (1.5 microM), CSH087 (3 microM) and CSH068 (3 microM) could prolong the action potential durations (APD50 and APD90). Voltage clamp studies revealed inhibition of the transient outward currents by S49, CSH087 and CSH068 with KD of 2.0, 1.8 and 5.2 microM, respectively, but a lack of enhancement of calcium influx. Therefore, the inhibition of the potassium conductance may explain the prolongation of APD induced by these compounds. In contrast, the late potassium outward current was more resistant to CSH087 and S49, but was blocked by CSH068 with a KD of 6.4 microM. The sodium inward current (INa) also was inhibited by S49, CSH087 and CSH068 in a dose-dependent manner with KD of 1.2, 6.8 and 7.5 microM, respectively (at a holding potential of -80 mV). The inhibition of INa) was enhanced at a less negative holding potential. The voltage-dependent inhibition of INa was associated with the shift of the INa availability curve to more negative potentials. These results indicate that these compounds have high affinity for inactivated Na+ channels. A twin-pulse experiment revealed that these compounds increased the recovery time constant of INa. The potency for the shift of the INa availability curve and the retardation of INa recovery from inactivation were S49 > CSH087 and CSH)68.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1993

Postnatal maturation of inwardly rectifying potassium current in isolated ventricular myocytes.

We have used the whole-cell voltage-clamp method to study the inwardly rectifying potassium channel in ventricular myocytes isolated from neonatal (N, < 3 days), infant (I, 10-17 days) and mature (M, > 3 months) rabbits. Currents were elicited by serial hyper- and de-polarization from a holding potential of -80 mV in the presence and absence of barium chloride (2 mM). Barium-sensitive currents, which showed properties of inward rectification and a reverse potential at -80 to -70 mV, actually reflected currents through inwardly rectifying potassium channels. The current-voltage relations and inward rectification occurring over the range of -50 to -10 mV were relatively similar in the three groups. However, the slope conductance of Ikl decreased and the extent of inward rectification increased with maturation. The slope conductance of Ikl was 3.45 +/- 0.42 nS/pF (n = 8) for N myocytes, 2.72 +/- 0.45 nS/pF (n = 11) for I myocytes and 1.28 +/- 0.19 nS/pF (n = 8) for M myocytes (p < 0.05 among the three groups and between each group). The greater slope conductance of Ikl is important in maintaining the electrical stability in smaller immature cells with larger axial resistance. The age-related changes of Ikl may contribute to the progressive lengthening of the action potential of myocytes. In summary, the present study has identified the maturation-associated changes of Ikl which are characterized by a decrease in slope conductance and an increase in the extent of inward rectification which can in part explain the transition of action potential characteristics.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Characterization of sodium inward currents and their responses to lidocaine in immature and mature rabbit ventricular myocytes.

Using the whole-cell voltage clamp method, sodium (Na) channel properties and their responses to lidocaine were studied in ventricular myocytes isolated from neonatal (N, < 3 days), infant (I, 10-17 days) and mature (M, > 3 months) rabbits. Developmental changes in the Na channels were characterized by a progressive right-shift in the inactivation curves and a faster recovery from inactivation. Lidocaine (10 microM) effectively reduced the peak Na currents in M myocytes, but had little affect on the current-voltage curve in N myocytes. The steady-state h inactivation curve shifted toward the left (ie, more negative potentials) after lidocaine, and the extent of the left-shift increased with maturation. Similarly, the magnitude of prolongation in Na channel recovery from inactivation by lidocaine increased with age. However, lidocaine at a higher concentration (30 microM) in N myocytes effectively blocked the Na channels, and the degree of suppression was comparable to that in M myocytes with 10 microM lidocaine. These data suggest that the Na channels of N myocytes per se are less sensitive to lidocaine. The results of this study indicate that the extent of Na channel inactivation becomes smaller during postnatal maturation. However, the Na channel of immature myocytes is less sensitive to the widely used Na channel blocker, lidocaine, which preferentially binds to the inactive state of the Na channel.

Age Factors↗
PubMed1992

Vasorelaxing effect in rat thoracic aorta caused by fraxinellone and dictamine isolated from the Chinese herb Dictamnus dasycarpus Turcz: comparison with cromakalim and Ca2+ channel blockers.

The components of Dictamnus dasycarpus Turcz were tested for their vasorelaxing effect on the rat aorta, and fraxinellone and dictamine were shown to be effective vasorelaxants. In high K+ (60 mmol/l) medium, Ca2+ (0.03 to 3 mmol/l)-induced vasoconstriction was inhibited concentration-dependently by both agents. The IC50 for fraxinellone and dictamine were calculated to be about 25 mumol/l and 15 mumol/l (for Ca2+ concentration of 1 mmol/l), respectively. Cromakalim (0.2-10 mumol/l) relaxed aortic rings precontracted with 15 but not 60 mmol/l of K+. Fraxinellone and verapamil were more potent and effective in producing relaxation in 60 mmol/l than in 15 mmol/l K(+)-induced contraction. However, dictamine was more potent in producing relaxation in 15 mmol/l K(+)-induced contraction. Nifedipine (1 mumol/l), dictamine (100 mumol/l) and fraxinellone (100 mumol/l) relaxed the aortic contraction caused by KCl or Bay K 8644. The tonic contraction elicited by noradrenaline (NA, 3 mumol/l) was also relaxed by dictamine (500 mumol/l), but not by fraxinellone (500 mumol/l) in the nifedipine (1 mumol/l)-treated aorta. This relaxing effect of dictamine persisted in endothelium-denuded aorta. Glibenclamide (10 mumol/l) shifted the concentration-relaxation curve of cromakalim, but not that of dictamine, to the right in rat aortic rings precontracted with NA. Dictamine (500 mumol/l) did not affect tonic contraction of NA which are reduced by H-7 (1 mumol/l) in Ca(2+)-depleted medium. In conclusion, fraxinellone is a selective blocker of voltage-dependent Ca2+ channel, while dictamine relaxed the rat aorta by suppressing the Ca2+ influx through both voltage-dependent and receptor-operated Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Going deep into chemical burns.

This is a five year retrospective study of chemical burn injury in our burn center between 1 January 1987 and 31 December 1991. Of the 1,226 total burn cases, 131 patients had chemical burns. We noted a constant prevailing incidence of 10.7% per year. Males (72%) are more common than females (28%). Most of those injured are in the working age group (65%). Majority of cases had deep full thickness burn involving less than 10% of their total body surface area. Sulfuric acid is the most common chemical agent encountered. We had three mortality cases with deep third degree burns covering 60% of their total body surface area. Some clinical cases are demonstrated. Lastly, proposed solutions for the prevention of chemical burns are cited.

Accidents, Occupational↗
PubMed1991

Bioactive principles from the roots of Lindera megaphylla.

d-Dicentrine was isolated from the root of Lindera megaphylla. It inhibited the aggregation of washed rabbit platelets induced by ADP, collagen, arachidonic acid, and PAF. It also inhibited the high potassium- and norepinephrine-induced contraction of rat thoracic aorta. In rat ventricular cells treated with 3 microM d-dicentrine, the action potential duration (ADP50) was prolonged from 59.9 +/- 11.3 msec to 201 +/- 28.7 msec.

Animals↗
PubMed1990

Polyadenylated RNA sequences from vaccinia virus-infected cells selectively inhibit translation in a cell-free system: structural properties and mechanism of inhibition.

The mechanism of vaccinia virus-induced selective inhibition of host cell protein synthesis was studied in a nonpermissive (Chinese hamster ovary, CHO) and in a permissive mouse cell line ( L cells). Small polyadenylated RNAs obtained from uninfected and infected cells were fractionated into six size classes by polyacrylamide gel electrophoresis. The RNAs from the first two largest fractions (greater than 500 nucleotide, nt) were translated into some low-molecular-weight polypeptides, whereas, the RNAs from the remaining fractions (400-500, 300-400, 200-300, and 100-200 nt) had no translational activity in reticulocyte lysates. When these nontranslating polyadenylated short sequences (POLADS) were added to the cell-free system together with HeLa cell mRNAs, translation was inhibited from 70%, by the 400- to 500-nt fraction, to about 20%, by the 100- to 200-nt fraction. The degree of inhibition of protein synthesis was clearly dependent on the size of POLADS. The translation of vaccinia virus mRNAs in the cell-free system was inhibited by about 25% with the 400- to 500-nt fraction, by 5% with the 300- to 400-nt fraction, while the smaller size POLADS had no inhibitory effect. The inhibition of HeLa cell and vaccinia virus mRNA translation by POLADS was reversed by the simultaneous addition of oligo(dT) to the cell-free system. POLADS were also obtained from uninfected cells, but they inhibited the translation of HeLa cell and vaccinia virus mRNAs to a much lesser extent. The removal of the poly(A) moiety from POLADS by treatment with ribonuclease H and oligo(dT) abolished their inhibitory effect on HeLa cell mRNA translation. The average length of the poly(A) tails of POLADS obtained from infected cells was longer than that of POLADS from normal cells. Inhibition of HeLa cell mRNA translation mediated by POLADS in the cell-free system was reversed (approximately 70%) by addition of crude initiation factors (ribosomal salt wash, RSW). Significantly, inhibition of translation of POLADS was reversed (greater than 90%) by addition of purified poly(A) binding protein (PAB). Purified initiation factor 4A (eIF-4A) also reversed this inhibition, but to a lesser extent than RSW and PAB. Our results show that the translation of vaccinia virus mRNAs is resistant to POLADS, suggesting that POLADS, by virtue of their long poly(A) tails, may sequester PAB and thus, play a role in selective inhibition.

Animals↗
PubMed1990

Comparison of the electrophysiological effect of amiodarone, lidocaine and quinidine on rat ventricular cells.

The effects of 20 microM each of amiodarone, lidocaine and quinidine on action potential and membrane currents were studied in rat ventricular cells. At a stimulation frequency of 0.1 Hz, quinidine prolonged the action potential duration (APD50) from 120 +/- 26 to 660 +/- 8 msec and increased the time to peak (Tp) amplitude from 7 +/- 1 msec to 32 +/- 6 msec. Lidocaine shortened APD50 from 123 +/- 15 to 83 +/- 6 msec without altering Tp. Amiodarone changed neither APD50 nor Tp. Voltage clamp study revealed that quinidine inhibited sodium inward current (INa) even when this current was elicited by depolarizing pulses at 0.1 Hz from a holding potential of -90 mV. For amiodarone and lidocaine, the inhibition was observed when INa was elicited from a holding potential of -70 mV. A frequency-dependent inhibition of INa by amiodarone and lidocaine was observed at frequencies higher than 1 Hz. Quinidine showed this inhibition even at 1 Hz. In correlation with the stronger frequency dependent inhibition of INa, a greater delay of the recovery and increase of the non-recovery fraction of INa was induced by quinidine. For lidocaine and amiodarone, only the recovery time constant was delayed. In cells treated with sea anemone toxin (ATX, 0.2 microM), APD50 was prolonged to 4-5 sec in 5 min. Quinidine, but not amiodarone, completely reversed the effect of ATX. Quinidine showed use-dependent inhibition of INa in these ATX-treated cells. Amiodarone, however, did not show this inhibition. It is likely that amiodarone suppresses INa by delaying the recovery of INa instead of blocking the open-state Na(+)-channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

Effects of quinidine and lidocaine on action potential and membrane currents of frog ventricles.

The effects of quinidine and lidocaine on frog ventricle were studied by using a single sucrose gap voltage clamp technique. In Ca2+-Ringer, quinidine (80 microM) caused slight prolongation of action potential duration (APD50) and significant inhibition of twitch tension. Lidocaine (40 microM) shortened APD50 without significant effect on twitch tension. In tetrodotoxin (TTX)-treated preparations, quinidine caused significant prolongation of APD50 from 529 +/- 19 msec to 597 +/- 11 msec, (n = 9) and inhibition of twitch tension, but lidocaine did not affect APD50 and twitch tension. Under voltage clamp condition, quinidine reduced peak inward current in the absence of TTX, but enhanced peak inward current in the presence of TTX. The steady state outward current was increased by quinidine. Lidocaine didn't affect peak inward current in the absence or in the presence of TTX. Membrane current through the inward rectifier (IK1) was slightly increased by lidocaine, but significantly inhibited by quinidine. The enhancement of peak inward current by quinidine was retarded or reversed in preparation bathed with Sr2+-Ringer. When Ni2+ was added to a preparation bathed in Ca2+-Ringer, an inhibition of calcium inward current and action potential plateau was observed. The spike amplitude of the action potential was, however, unaffected by Ni2+. In this Ni2+-treated preparation, lidocaine (20 microM) caused significant shortening of APD50 without significant effect on action potential amplitude. The shortening of APD50 was associated with a slight increase of steady state outward current. The increase of steady state outward current by lidocaine was absent in the TTX-treated preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗