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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 339, Issue 4, pp 441–447 | Cite as

Sodium channel-blocking properties of flecainide, a class IC antiarrhythmic drug, in guinea-pig papillary muscles An open channel blocker or an inactivated channel blocker

  • Michio Kojima
  • Takuyuki Hamamoto
  • Takashi Ban
Article

Summary

Effects of flecainide (a class IC antiarrhythmic drug) on the maximum rate of rise (\(\dot V_{\max } \)) of action potentials (APs) were studied in guinea-pig papillary muscles, with special reference to their time, voltage, and action potential duration (APD) dependence in the presence and absence of nicorandil. Nicorandil was used to shorten APD, i.e., the time period of inactivation state of sodium channels. APs were recorded from the preparations using standard microelectrode techniques. Flecainide (5 μmol/l) reduced\(\dot V_{\max } \) without changing resting potential, AP amplitude, APD50, and APD90 examined at 1 Hz. The drug shifted the normalized\(\dot V_{\max } \)-membrane potential curve (examined at 1/60 Hz) in the hyperpolarizing direction by 3.1 ± 0.8 mV (n = 6) (voltage dependence). The drug caused a frequency-dependent reduction of\(\dot V_{\max } \) at ≥ 0.1 Hz, developed a use-dependent reduction of\(\dot V_{\max } \) at 1 Hz with an onset time constant of 11.7 ± 0.4 s (n = 6), and slowed the recovery process of\(\dot V_{\max } \), whose resultant recovery time constant was 19.9 ± 1.2 s (n = 6) (time dependence). These flecainide-induced time-dependent reductions of\(\dot V_{\max } \) were not antagonized by nicorandil (1 mmol/1) which shortened APD to about 1/4 of control (APD independence). These results suggest that flecainide is primarily an open channel blocker because its channel-blocking actions are independent of APD or the time period of inactivation.

Key words

Flecainide Class I antiarrhythmic drugs Time, voltage, and APD dependence of sodium channel block Guinea-pig papillary muscles Cardiac electrophysiology 

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Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Michio Kojima
    • 1
  • Takuyuki Hamamoto
    • 1
  • Takashi Ban
    • 1
  1. 1.Department of Pharmacology, School of MedicineYamaguchi UniversityUbe, YamaguchiJapan

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