Positive inotropic effect of 4-aminopyridine on dog ventricular muscle

T. Yanagisawa, N. Taira

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

1. In trabecular muscles obtained from the right ventricle of untreated dogs 4-aminopyridine (4-AP) (0.1-10 mM) increased the force of contraction elicited by electrical driving at 0.5 Hz. 2. This effect was associated with increases in mean velocities of force development and relaxation. The time to peak force was not changed by 4-AP and the relaxation time was increased by 3 and 10 mM 4-AP. 3. In ventricular muscles treated with the β-adrenoceptor blocking agent, pindolol, or in those obtained from dogs pretreated with reserpine the positive inotropic effect was reduced. 4. In such muscles 4-AP scarcely increased the mean velocity of force development and slightly increased the time to peak force. Marked prolongation of the relaxation time and a decrease in mean velocity of relaxation were characteristic of isometric contractions of such muscles in the presence of 4-AP. 5. These results indicate that the positive inotropic effect of 4-AP is sum of two effects, one being due to the release of endogenous catecholamines and the other to a possible direct action on cardiac muscle. 6. In muscles treated with pindolol or those obtained from dogs pretreated with reserpine 10 mM 4-AP elevated the resting force. 7. These observations suggest that 4-AP causes a persisting elevation of cytosolic Ca2+ in cardiac muscle cells. 8. In pindolol-treated muscles 4-AP prolonged the action potential duration. However, the prolongation of the action potential duration produced by 4-AP was much smaller than that of the relaxation time. Even with 10 mM 4-AP the resting membrane potential remained unchanged. 9. The above results suggest that the effects of 4-AP on the contraction and resting force of ventricular muscle may not be secondary to the effect on the transmembrane potential. 10. All the results taken together suggest that the primary action of 4-AP on ventricular muscle may not be to allow increased or prolonged entry of extracellular Ca2+ but rather may be either to promote the release of Ca2+ from intracellular binding or storage sites or to slow the binding of Ca2+ to intracellular structures. The prolongation of the action potential duration may be a consequence of change in calcium binding to the plasma membrane.

Original languageEnglish
Pages (from-to)207-212
Number of pages6
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume307
Issue number3
DOIs
Publication statusPublished - 1979 Jul 1

Keywords

  • 4-Aminopyridine
  • Action potential
  • Calcium
  • Cardiac muscle
  • Catecholamines
  • Relaxation

ASJC Scopus subject areas

  • Pharmacology

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