Effects of potassium conductance inhibitors on spontaneous diastolic depolarization and abnormal automaticity in human atrial fibers

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Abstract
The capability of generating spontaneous diastolic depolarization and automaticity was investigated in vitro by means of standard microelectrode techniques in 50 human atrial preparations. Samples were classified within two groups: (i) group 1 was composed of 12 well-polarized preparations exhibiting action potentials that were fast responses (mean maximum diastolic potential:−75.5 mV and Vmax greater than 100V);(ii) group 2 was composed of 38 partially-depolarized samples (mean maximum distolic potential: −50.3 mV and Vmax less than 10 V/s) and was further divided into two subgroups. Subgroup 2A consisted of 20 spontaneously beating preparations and subgroup 2B consisted of 18 non-automatic partially-depolarized specimens. Highly-polarized fibers from group 1, although exhibiting a slight diastolic depolarization which was almost entirely suppressed by 2 mM cascium, never presented spontaneous activity under our experimental conditions. 90% of automatic fibers from subgroup 2A were sampled from dilated atria. In automatic preparations, diastolic depolarization was usually separated into two phases: an initial phase, also present in non-automatic fibers, and a late phase. Changes in the initial phase were not accompanied by concomitant changes in the spontaneous rate. Abnormal automaticity was clearly related to the late diastolic phase (absent in non-automatic fibers), the generation of which appeared to be specific property of automatic fibers. The use of K conductance inhibitors (caesium, 4-aminopyridine, barium, low K solutions) provided indirect evidence that neither delayed outward ix current nor it type inward current are principally responsible for abnormal automaticity.