Academic Journal
Suppression of time-dependent outward current in guinea pig ventricular myocytes. Actions of quinidine and amiodarone.
| العنوان: | Suppression of time-dependent outward current in guinea pig ventricular myocytes. Actions of quinidine and amiodarone. |
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| المؤلفون: | Balser, J R, Bennett, P B, Hondeghem, L M, Roden, D M |
| المصدر: | Circulation Research ; volume 69, issue 2, page 519-529 ; ISSN 0009-7330 1524-4571 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health) |
| سنة النشر: | 1991 |
| الوصف: | Prolongation of cardiac action potentials may mediate some of the arrhythmia-suppressing and arrhythmia-aggravating actions of antiarrhythmic agents. In this study, suppression of time-dependent outward current by quinidine and amiodarone was assessed in guinea pig ventricular myocytes. The net time-dependent outward current contained at least two components: a slowly activating, La(3+)-resistant delayed rectifier current (IK) and a rapidly activating, La(3+)-sensitive current. Quinidine block of total time-dependent outward current during clamp steps to positive potentials was relieved as a function of time, whereas that induced by amiodarone was enhanced. In contrast, at negative potentials, suppression of current, whereas amiodarone reduced IK but not the La(3+)-sensitive current, suggesting that differential block of the two components of time-dependent current underlies the distinct effects of the two agents. In contrast to these disparate effects on total time-dependent outward current, steady-state reduction of IK by both drugs increased at positive voltages and saturated at approximately +40 mV; the voltage dependence of block by quinidine (17% per decade, +10 to +30 mV) was steeper than that by amiodarone (5% per decade, +10 to +20 mV). Block by quinidine was time dependent at negative potentials: on stepping from +50 to -30 mV, block initially increased very rapidly, and subsequent deactivation of IK was slowed. This effect was not seen with amiodarone. At -80 mV, quinidine block was relieved with a time constant of 40 +/- 15 msec (n = 4, twin-pulse protocol). The effects of quinidine on IK were compatible with neither a purely voltage-dependent model of quinidine binding nor a model incorporating both voltage- and state-dependent binding of quinidine to delayed rectifier channels having only one open state. The voltage- and time-dependent features of quinidine block were well described by a model in which quinidine has greater affinity for one of two open states of the channel. We conclude that the ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1161/01.res.69.2.519 |
| DOI: | 10.1161/01.RES.69.2.519 |
| الاتاحة: | http://dx.doi.org/10.1161/01.res.69.2.519 https://www.ahajournals.org/doi/pdf/10.1161/01.RES.69.2.519 |
| رقم الانضمام: | edsbas.CB9A0174 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1161/01.res.69.2.519 |
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