Key result
High-frequency electrical stimulation (overdrive at 6.7 Hz) reduced the L-type calcium current by 85% at a holding potential of -40 mV, suggesting its slow inactivation plays a key role in overdrive suppression.
Why the study?
Does high-frequency stimulation induce overdrive suppression via slow inactivation of L-type calcium current in isolated rabbit sinoatrial node cells?
Does high-frequency stimulation induce overdrive suppression via slow inactivation of L-type calcium current in isolated rabbit sinoatrial node cells?
Voltage-dependent slow inactivation of the L-type calcium current plays a central role in the mechanism of overdrive suppression in sinoatrial node cells.
Supports voltage-dependent L-type Ca current inactivation in rabbit SAN overdrive suppression; leaves open translation to human sinus node physiology.
自発興奮を示すウサギ単離洞結節細胞にwhole-cell clamp法の膜電流固定モードで高頻度刺激 (overdrive) を加えると一時的な自動能抑制 (overdrive suppression) が生じた.Overdrive後の膜電位変化としては最大拡張期電位減少に加えて, 活動電位overshootと最大立ち上がり速度 (Vmax) の減少が認められた.膜電位固定実験 (TTX作用下) では, 保持電位-40mVからの脱分極パルス (0mV, 100ms) の頻度を1HZから6.7HZに上げるとL型Ca電流 (ica) が一拍毎に減少し, 30秒後には平均85%減少した.パルス頻度を1Hzに戻すとicaは比較的速やかに回復した (時定数5.6s) .保持電位-80mVの場合は, 高頻度パルス中のica減少は軽度であった (平均29%) .膜電流固定モードから一時的に膜電位固定モードに切り換え, 高頻度脱分極パルスを与える実験では, 保持電位-40mVの場合は高頻度パルス中のica減衰に続いて, 自発興奮抑制が生じた.保持電位-80mVの場合はica減衰も自発興奮抑制も生じなかった.遅延整流K電流 (iK) と過分極活性化電流 (if) は高頻度脱分極パルスの前後で殆ど変化しなかった.洞房結節におけるoverdrive suPPressionにicaの膜電位依存性緩徐不活性化が重要な役割を果たすことが示唆された. (心電図16: No.4, 317～323, 1996)
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Kodama et al. (1996) studied Normal sinoatrial node electrophysiology. High-frequency electrical stimulation (overdrive) vs. Baseline stimulation (1 Hz) was evaluated on L-type calcium current (iCa) reduction. High-frequency electrical stimulation (overdrive at 6.7 Hz) reduced the L-type calcium current by 85% at a holding potential of -40 mV, suggesting its slow inactivation plays a key role in overdrive suppression.
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