ISSN:
1615-2573
Keywords:
Amrinone
;
Sinoatrial node
;
Phosphodiesterase inhibitor
;
Membrane ionic current
;
Chronotropic action
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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 × 0.2 × 0.1mm) of rabbit sinoatrial (SA) node cells. Amrinone (0.1–1.0mM) 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, 0.1mM amrinone increased the Ca2+ current (I Ca) obtained on step depolarization from −40 to −10mV by 25.86% ± 4.6% (P 〈 0.05,n = 6), the delayed rectifier K+ current (I K) tail obtained on repolarization from 10 to −60mV by 22.8% ± 4.7% (P 〈 0.05,n = 6), and the hyperpolarization-activated inward current (I h) at −90mV by 19.5% ± 7.3% (P 〈 0.05,n = 6), respectively. Amrinone did not affect the slope factors of either the inactivation curve forI Ca (f∞ curve) or the activation curve for the delayed rectifierI 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01747828
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