심근 수축에 있어서 Calcium 이온의 기원에 관한 약리학적 연구

Abstract

Na-Ca exchange transports calcium ion either into (reverse mode Na-Ca exchange) or out of the cell (forward mode Na-Ca exchange) according to the direction of driving force produced by the changes in ratio of intra- and extra-cellular Na concentrations. Thus, Na-Ca exchange is regarded as the regulator of myocardial contraction. However, the existence of reverse mode Na-Ca exchange and its role in myocardial contraction is still questioned. Present study was performed to identify the presence of reverse mode Na-Ca exchange and its possible involvement in the regulation of myocardial contraction in rat heart. Using the left atria of rat, contraction was induced by electrical field stimulation (EFS, 0.5 msec duration and supramaximal voltage). Changing of the stimulation frequencies from resting 4 Hz to 0.4, 1 or 8 Hz caused typical negative staircase effect in twitch tension, but uptake showed bimodal increase. When the stimulation frequency was abruptly changed from 4 Hz to 0.4 Hz the atrial twitch tension showed three phased-enhancement, that is, the initial rapid increase (the first phase) followed by rapid decrease (the second phase) and stabilization (the third phase). uptake was equivalent to tension, i.e. initial significant increase in first 30 second and then decrease. Benzamil treatment abolished the first phase of increase in a dose dependent manner from Bay k 8644 treatment enhanced the inotropy induced by frequency reduction and abolished the second and third phase decreases. Benzamil treatment also suppressed the contraction stimulated by Bay K 8644. Although the contraction at 4 Hz stimulation was completely abolished by verapamil pretreatment, the contraction reappeared as soon as the stimulation frequency was changed into 0.4 or 1 Hz and interstingly, uptake were significantly higher than no treatment. From these results, it is concluded that reduction of stimulation frequency causes calcium influx by the reverse mode Na-Ca exchange, resulting in initial rapid increase of twitch tension. then it turns into forward mode exchange to efflux the calcium, resulting in decrease of the twitch tension in left atria of rat.