Electrophysiological effects of amrinone on the automaticity and membrane current system of the rabbit sinoatrial node cells

Tadayoshi Hata, Masao Nishimura, Kayo Ogino, Hirohide Uchiyama, Yoshio Watanabe

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Abstract

To elucidate the physiological role of phosphodiesterase (PDE) in cardiac pacemaker cells, we studied the electrophysiological effects of amrinone, an inhibitor of PDE type III, on the spontaneous action potential (AP) and membrane currents, using small preparations (0.2 x 0.2 x 0.1 mm) of rabbit sinoatrial (SA) node cells. Amrinone (0.1-1.0 mM) progressively increased the AP amplitude, maximal rate of depolarization, and spontaneous firing frequency, shortened the AP duration, and made the threshold potential more negative. In voltage-clamp experiments using double microelectrode techniques, 0.1 mM amrinone increased the Ca2+ current (I(Ca)) obtained on step depolarization from -40 to -10 mV by 25.86% ± 4.6% (P < 0.05, n = 6), the delayed rectifier K+ current (I(K)) tail obtained on repolarization from 10 to -60 mV by 22.8% ± 4.7% (P < 0.05, n = 6), and the hyperpolarization-activated inward current (I(h)) at -90 mV by 19.5% ± 7.3% (P < 0.05, n = 6), respectively. Amrinone did not affect the slope factors of either the inactivation curve for I(Ca) (f(∞) curve) or the activation curve for the delayed rectifier I(K) (p(∞) curve). These results suggest that this PDE III inhibitor exerts a positive chronotropic action by enhancing the availability and the conductance of all the tested membrane currents in rabbit SA node cells.

Original languageEnglish
Pages (from-to)114-121
Number of pages8
JournalHeart and Vessels
Volume13
Issue number3
DOIs
Publication statusPublished - 01-01-1998

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All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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