Amantadine-induced afterpotentials and automaticity in guinea pig ventricular myocytes

M. Hiraoka, Y. Hirano, S. Kawano, Zheng Fan, T. Sawanobori

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The ionic mechanisms of amantadine-induced changes in membrane potential and automatic activity in guinea pig ventricular myocytes were studied using the suction-pipette whole-cell clamp method. While 25-100 μM amantadine decreased the action potential amplitude and duration, 200 and 400 μM amantadine lengthened the action potential duration and decreased the maximum diastolic potential with an appearance of diastolic depolarization and automaticity. In the presence of 25-100 μM amantadine, the preparations developed an afterpotential due to incomplete repolarization and a delayed afterdepolarization that eventually brought about triggered automaticity. The former type of afterpotential was abolished by tetrodotoxin (TTX) and the latter by Co2+. Spontaneous activity from the diastolic depolarization was also abolished by Co2+ but not by Cs+. Amantadine suppressed the calcium current to as much as half of the control at the concentrations used (25-200 μM). The drug also produced a depression of the inward rectifier K+ current. The outward current showing time-dependent decay was activated at the plateau voltages by concentrations lower than 100 μM, whereas the delayed outward K+ current was depressed by the drug in a concentration-dependent manner at more positive potentials. Amantadine activated the TTX-sensitive and TTX-insensitive inward currents on repolarization from depolarized states, without producing the transient inward current. These results indicate that the amantadine-induced diastolic depolarization and afterpotentials are caused by changes in multiple ionic currents and that, therefore, the drug can be used as a unique model for the study of arrhythmogenesis.

Original languageEnglish (US)
Pages (from-to)880-893
Number of pages14
JournalCirculation research
Volume65
Issue number4
DOIs
StatePublished - Jan 1 1989
Externally publishedYes

Fingerprint

Amantadine
Muscle Cells
Guinea Pigs
Tetrodotoxin
Action Potentials
Pharmaceutical Preparations
Suction
Membrane Potentials
Calcium

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Amantadine-induced afterpotentials and automaticity in guinea pig ventricular myocytes. / Hiraoka, M.; Hirano, Y.; Kawano, S.; Fan, Zheng; Sawanobori, T.

In: Circulation research, Vol. 65, No. 4, 01.01.1989, p. 880-893.

Research output: Contribution to journalArticle

Hiraoka, M. ; Hirano, Y. ; Kawano, S. ; Fan, Zheng ; Sawanobori, T. / Amantadine-induced afterpotentials and automaticity in guinea pig ventricular myocytes. In: Circulation research. 1989 ; Vol. 65, No. 4. pp. 880-893.
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