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Effects of class Ic antiarrhythmic agent, pilsicainide, on sodium current in isolated guinea pig ventricular myocytes
https://kindai.repo.nii.ac.jp/records/2002987
https://kindai.repo.nii.ac.jp/records/20029874d2848b5-8aa9-416e-a51e-3756d3072384
| 名前 / ファイル | ライセンス | アクション |
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AA0050842X-19970300-0055.pdf (966.5 KB)
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| アイテムタイプ | 紀要論文 / departmental bulletin paper(1) | |||||||
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| 公開日 | 2025-06-23 | |||||||
| タイトル | ||||||||
| タイトル | Effects of class Ic antiarrhythmic agent, pilsicainide, on sodium current in isolated guinea pig ventricular myocytes | |||||||
| 言語 | en | |||||||
| 作成者 |
Sugano, Makoto
× Sugano, Makoto
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| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題 | whole cell patch clamp technique, sodium current, pilsicainide, tonic block, phasic block, recovery from phasic block | |||||||
| 内容記述 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Background : In discussing the antiarrhythmic effects of drugs, the mechanism is often evaluated by taking into account the processes of association and dissociation between such drugs and their receptor sites. In the present study we examined the blockade of sodium current (INa) in isolated guinea pig ventricular myocytes by pilsicainide and the dissociation of pilsicainide from sodium channels. Method : Hearts from male guinea pigs were perfused by Langendorff's method to prepare isolated ventricular myocytes using collagenase. Membrane currents of the isolated ventricular myocytes were recorded using the whole cell patch clamp technique with a patch aspirating electrode. Results : Pilsicainide had no effect on the threshold, peak and equilibrium potentials of INa, but it decreased INa to 62.8±0.6% of the baseline value on average. Pilsicainide decreased INa in a concentration-dependent manner, with the Kd value of 49.9±2.3 μmol/l at a holding potential of -140 mV, and the Kd of 5.5±0.6 μmol/l at -100 mV. This drug shifted thd steady-state inactivation curve by -14.9±1.8 mV to the hyperpolarized direction along the voltage axis without changes in the slope factor. The higher the depolarization frequency, and the longer the depolarization duration, the more pilsicainide decreased INa. The time constant of the onset of the phasic block of INa by pilsicainide were the fast phase time constant (τfast) of 4.5±0.4 msec and the slow phase time constant (τslow), of 183.6±5.6 msec. The onset of phasic block of INa with removal of the fast component of INa inactivation, had a time constant of 206.3±12.7 msec. The time constants of the fast and slow phases of recovery from phasic block were 11.2±1.3 msec and 37.0±2.7 sec at a holding potential of -140 mV, respectively, and were 16.5±1.9msec and 42.7±3.4 sec at a holding potential of -120 mV, respectively. Conclusion : Pilsicainide induced tonic and phasic blocks of INa in a concentration-dependent manner without affecting sodium channel kinetics. It could be interpreted that INa fast inactivation is not essential for phasic blocks induced by this drug. These findings also suggest that the dissociation of the phasic block of pilsicainide from receptor sites takes place via the hydrophobic pathway. | |||||||
| 言語 | en | |||||||
| 出版者 | ||||||||
| 出版者 | The Kinki University Medical Association | |||||||
| 言語 | en | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||
| 資源タイプ | departmental bulletin paper | |||||||
| 出版タイプ | ||||||||
| 出版タイプ | AM | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||||
| 収録物識別子 | ||||||||
| 収録物識別子タイプ | PISSN | |||||||
| 収録物識別子 | 03866092 | |||||||
| 開始ページ | ||||||||
| 開始ページ | 55 | |||||||
| 終了ページ | ||||||||
| 終了ページ | 65 | |||||||
| 書誌情報 |
en : ACTA MEDICA KINKI UNIVERSITY 巻 22, 号 1, p. 55-65, 発行日 1997-03 |
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