We studied the effects of AN-132 (10, 30 and 100 mumol/l), an analogue of lidocaine, on membrane currents and action potentials of single guinea-pig ventricular cells using whole-cell clamp techniques. The effects of lidocaine, an authentic class I antiarrhythmic agent were used for comparative purposes. (1) AN-132 decreased the Na current (INa) in a concentration-dependent manner, with a greater efficacy than seen with lidocaine. The concentration of the half maximal inhibition on INa (Kd) was 31.7 mumol/l for AN-132 and 94.9 mumol/l for lidocaine. (2) AN-132 also decreased the Ca current (ICa), concentration-dependently, while lidocaine had only a minor effect on ICa. The half maximal inhibition on ICa (Kd) was 23.1 mumol/l and 27.4 mumol/l for AN-132 and lidocaine, respectively. (3) AN-132 decreased the IK1, in a concentration-dependent manner; lidocaine was without effect. (4) AN-132 increased the unspecified steady state outward current, at positive potentials and depressed the time- and voltage-dependent outward K current (IK). Lidocaine had no effect on either current. (5) AN-132 shortened the action potential duration (APD), in a concentration-dependent manner, without altering the resting potential. From these findings, we conclude that apart from a potent inhibitory effect on INa, AN-132 had a variety of effects on other currents, properties not shared by lidocaine. Such multiple blocking effects on the membrane currents may relate to the alleged potent antiarrhythmic effect of AN-132.

Anilides↗

PubMedDate not supplied

Association of insulin with QTc dispersion.

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Blood Glucose↗

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Mechanism of fluoride action on the L-type calcium channel in cardiac ventricular myocytes.

The modulatory actions of fluoride on the function of the dihydropyridine-sensitive (L-type) Ca2+ channel were studied in rabbit cardiac myocytes. In cell-attached voltage-clamp experiments, using barium as the charge carrier, fluoride increased the activity of the Ca2+ channel dose-dependently. Low concentrations (<10 mM) of fluoride increased the number of traces with channel activities, and decreased the number of traces without channel activities, resulting in a net increase in the open-channel probability. The effect of 5 mM fluoride on the Ca2+ channel was inhibited by the presence of non-hydrolyzable guanosine diphosphate analog in the cell. On the other hand, high concentrations (>10 mM) of fluoride increased the open-channel duration, resulting in a marked increase in open-channel probability. A pretreatment of myocytes with a phosphatase inhibitor, okadaic acid, virtually abolished the additional effect of fluoride on the open-channel duration or open probability. A concentration of up to 75 mM fluoride had no effect on the Ca2+-channel activity when the myocytes were pretreated with a potent inhibitor of protein kinases, indicating that fluoride increased the Ca2+- channel activity via modulation of the phosphorylation state of the myocyte or the channel protein alone.

Animals↗

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Antiarrhythmic effects of nicorandil on canine cardiac Purkinje fibers.

Antiarrhythmic efficacy of nicorandil (SG-75) (1-100 microM), a coronary vasodilator, was investigated electrophysiologically with regard to the action potentials of canine Purkinje fibers. The main results obtained are as follows: (a) nicorandil suppressed three kinds of automaticities, i.e., spontaneous or low-K+-induced automaticity and electrical depolarization-induced automaticity; (b) the drug increased the effective refractory period relative to action potential duration and decreased differences between action potential duration and effective refractory period; and (c) in the presence of nicorandil (50 microM), membrane potentials at which the earliest premature response could be elicited were significantly more negative than control, thus leading to a much faster upstroke velocity of the premature response. These changes in electrophysiological properties suggest that the drug may be effective for treating selected cardiac arrhythmias due to both enhanced automaticity and reentry, particularly in the presence of a decreased membrane K conductance. These effects of nicorandil could be mostly attributed to an increase in membrane K conductance.

Action Potentials↗

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Purification and partial characterization of a hemagglutinating factor (HAF): a possible adhesive factor of the diffuse adherent of Escherichia coli (DAEC).

The mannose-resistant hemagglutinating factor (HAF) was extracted and purified from a diffuse adherent Escherichia coli (DAEC) strain belonging to the classic enteropathogenic E. coli (EPEC) serotype (0128). The molecular weight of HAF was estimated to be 18 KDa by SDS-PAGE and 66 KDa by Sephadex G100, suggesting that the native form of HAF consists of 3-4 monomeric HAF. Gold immunolabeling with specific HAF antiserum revealed that the HAF is not a rigid structure like fimbriae on the bacterial surface. The immunofluorescence test using purified HAF on HeLa cells, in addition to the fact that the HAF is distributed among serotypes of EPEC, suggests that HAF is a possible adhesive factor of DAEC strains.

Adhesins, Escherichia coli↗

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Electrically induced automaticity in canine ventricular myocardium.

Repetitive spontaneous action potentials (SAP) could be induced in canine ventricular and atrial muscle, although this inhibitory action was antagonized by the pretreatment with voltage range between about -60 mV and 0 mV. The SAP seemed dependent on both slow inward Ca2+ and Na+ currents and was suppressed by verapamil, Mn2+, and diltiazem, but not by tetrodotoxin. The increase of extracellular potassium concentration also suppressed the SAP. Acetylcholine could not block the SAP in ventricular muscle, but inhibited that in atrial muscle, although this inhibitory action was antagonized by the pretreatment with atropine. The automatic activity was attributed to slow inward Ca2+ and Na+ currents modified by decreasing time-dependent K+ outward current and K+ anomalous rectification.

Action Potentials↗

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Intraventricular conduction disturbance due to delayed recovery from ventricular inactivation in chlorpromazine-treated dogs.

In in situ canine hearts, chlorpromazine induced a time (preceding cycle length)-dependent decrease in conduction velocity within the ventricle. Thus, QRS duration of nonpremature beats was lengthened at rapid pacing rates while QRS duration of atrial premature beats was lengthened at short coupling intervals. These slow conductions were not due to reduced take-off potential of ventricular action potentials but to drug-induced slow recovery of the rapid Na+ system. The phenomenon may be responsible for reported QRS prolongation and fatal ventricular arrhythmias encountered in patients receiving phenothiazines.

Action Potentials↗