| Budget Amount *help |
¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1986: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1985: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Research Abstract |
Triggered-activity is one of important cellular factors for the genesis of arrhythmias. The membrane potential changes to produce triggered-activity are brought by several different mechanisms depending on the experimental conditions. To clarify the nature and the ionic mechanism of these potential changes, the microelectrode technique and voltage clamp method of the single sucrose gap or whole-cell clamp were applied to heart cells from dog, guinea pig, rabbit and frog. In the <Ca^(2+)> -overloaded conditions by exposing to the low <K^+> , high <Ca^(2+)> solutions, triggered-activity was caused by delayed afterdepolarization which was formed by the transient inward current. The characteristics of these delayed afterdepolarizations and the transient inward current were fully analyzed in terms of the responses to the electrical stimulation, as well as their voltage and time dependent natures. These informations may be used as diagnostic clues for the clinical arrhythmias based on these
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activities but different from reentry or automaticity. The study also disclosed that the transient inward current was activated not only upon repolarization but also during the depolarizing voltages, reflecting cyclic release of <Ca^(2+)> from the sarcoplasmic reticulum. The contribution of <Ca^(2+)> influx via the slow channel to the activation of the transient inward current was demonstrated by use of the <Ca^(2+)> blockers and their actions on triggered-arrhythmias can be explained by the inhibition of the <Ca^(2+)> current. The increase in the internal longitudinal resistance during the development of the delayed afterdepolarizations and triggered-activity was demonstrated by the cable analysis. The study demonstrated that the barium-induced delayed afterdepolarization and automaticity were not brought by the activation of the transient inward current, but by the <Ba^(2+)> action on the inward rectifier <K^+> current ( <I_(kl)> ). <Ba^(2+)> produced time- and voltage-dependent blockade of <I_(kl)> , which induced the delayed afterdepolarizations and automaticity. Aconitine is another agent to produce delayed afterdepolarizations and triggered-activity. In this case, the transient inward current which was triggered by the <Na^+> loading by aconitine, was shown to be a contributing factor. Therefore, triggered-activity is brought not by a single ionic mechanism, but by several different mechanisms, which may explain complex natures of these arrhythmias. Less
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