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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 344, Issue 3, pp 331–336 | Cite as

Aprindine blocks the sodium current in guinea-pig ventricular myocytes

  • Ryoichi Sato
  • Ichiro Hisatome
  • Yasunori Tanaka
  • Norito Sasaki
  • Hiroshi Kotake
  • Hiroto Mashiba
  • Ryo Katori
Original Articles

Summary

Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 µmol/l) on the Na+ current using whole cell voltage clamp (tip resistance = 0.5 Ω, [Na]i ando = 10 mmol/l at 18°C). Aprindine revealed tonic block (Kdrest = 37.7 µmol/l, Kdi = 0.74 µmol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 ± 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 µmol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% ±3070 at 1.5 ms, 82%±6% at 20 ms, 93%±7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na+ current by 3 mmol/l tosylchloramide sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = −100 mV and 5.0 s at holding potential = –140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 µmol/l aprindine showed smaller use-dependent block (14% ± 7% at 2 Hz; n = 4) comparing with either at pH 7,4 (68% ± 13%; n = 4) or at pH 8.0 (90% ±12%; n = 4).

The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

Key words

Sodium channel Aprindine Modulated receptor hypothesis Deprotonation 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Ryoichi Sato
    • 1
  • Ichiro Hisatome
    • 2
  • Yasunori Tanaka
    • 2
  • Norito Sasaki
    • 2
  • Hiroshi Kotake
    • 2
  • Hiroto Mashiba
    • 2
  • Ryo Katori
    • 1
  1. 1.1st Department of MedicineKinki UniversityOsakaJapan
  2. 2.1st Department of MedicineTottori UniversityYonagoJapan

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