• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.707-716
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• 1997

Recent reports revealed that the $Na^+-Ca^{2+}$ exchangers and feet structures of sarcoplasmic reticulum(SR) are located in close vicinity in the specific compartment. Therefore, we investigated the possibility that the $Na^+-Ca^{2+}$ exchanger may decrease the tension development by transporting the $Ca^{2+}$ out of the cell right after it released from SR, on the basis of this anatomical proximity. We exammined the negative force-frequency relationship of the developed tension in the electrically field stimulated left atria of postnatal developing rat(1, 3 day, 1 week and 4 week old after birth). Cyclopiazonic $acid(3{\times}10^{-5}\;M)$ treatment decreased the developed tension further according to postnatal age. $Monensin(3{\times}10^{-6}\;M)$ treatment did not increase the maximal tension in 4 week-old rat, preserving negative staircase, while the negative staircase in the younger rat were flattened. $Ca^{2+}$ depletion in the buffer elicited more suppression of the maximal tension according to the frequency in all groups except the 4 week-old group. The % decrease of the maximal developed tension of 4 week-old group at 1 Hz to that of 0.1 Hz after $Na^+$ and $Ca^{2+}$ depletion was only a half of those of the yonger groups. Taken together, it is concluded that the $Na^+-Ca^{2+}$ exchange transports more $Ca^{2+}$ released from SR out of the cell in proportion to the frequency, and this is responsible for the negative staircase effect of the rat heart.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.715-724
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• 1998

Frequency-force relationships (FFR) were studied in electrically field stimulated rat left atria (LA) by reducing the stimulation frequency from resting 3 Hz to test frequencies (0.1-1 Hz) for 5 minutes. The twitch amplitudes of LA elicited the typical negative staircases with 3-phased changes: the initial rapid increase, the second decrease and the following plateau at test frequencies. Verapamil $(3{\times}10^{-5}\;M)$ pretreatment elicited frequency-dependent suppression of the twitch amplitudes, exaggerating the negative staircase. Monensin pretreatment enhanced not the peak but the plateau amplitudes in a concentration-dependent manner. When the $Na^+-Ca^{2+}$ exchange was blocked by $Na^+\;and\;Ca^{2+}$ depletion in the Krebs Hensleit buffer (0 $Na^+-0\;Ca^{2+}$ KHB), the twitch amplitudes increased in a frequency-dependent manner, changing the negtive staircase into the positve one. Meanwhile, the 0 $Na^+-0\;Ca^{2+}$ KHB applicationinduced enhancement was strongly suppressed by caffeine (5 mM) pretreatment. Only dibucaine among the local anesthetics increased the basal tone during frequency reduciton. There were no differences in $^{45}Ca$ uptakes between 0.3 Hz and 3 Hz stimulation except at 1 min when it was significantly low at 0.3 Hz than 3 Hz, illustrating net $Ca^{2+}$ losses. Monensin pretreatment enhanced the rate of this $Ca^{2+}$ loss. Taken together, it is concluded that $Na^+-Ca^{2+}$ exchange extrudes more SR released $Ca^{2+}$ out of the cell in proportion to the frequency, resulting in the negative rate staircase in the rat LA.

• The Korean Journal of Physiology
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• 제23권2호
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• pp.301-312
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• 1989

It well known that the magnitude of contraction and the shape of action potential depend upon the stimulation frequency and the duration of resting period (positive and negative staircase). Although the underlying mechanism of the staircase phenomenon is not fully understood, it has been suggested that staircase could be related to the intracllular $Ca^{2+}$ concentration. In order to elucidate the role of intracellular $Ca^{2+}$ on the contraction and action potential staircases, we examined the effects of 1 mM 4-aminopyridine (4-AP), 0.5 uM verapamil, 1 uM ryanodine, or reduction of extracellular Na concentration to 30% $(substituted\;by\;equimolar\;Li^+)$ in small atrial strips of the rabbit $(3{\times}10\;mm)$. The results obitained were as follows; 1) When the stimulation frequency was increased from 0.1 Hz to 2 Hz, positive staircase of the contraction and elevation of plateau level in action potential were found in control and the conditions of Na reduction and treatments of 4-AP, verapamil and ryanodine. 2) When stimulation frequency returned to 0.1 Hz from 1 min rest just after 2 Hz stimulation fer 1 min, the magnitudes of initial few contractions were larger than that of steady state contraction (post-rest potentiation) except, ryanodine or Na-reduction groups. 3) Negative staircase of contraction was developed in control and 4-AP group at post-rest 0.1 Hz stimulation and the plateau level of the action potential was decreased at the same time. But the reduction of contraction or the plateau level was much smaller in 4-AP group and than in control. From the above results it can be concluded that contraction and action potential staircase is dependent upon transmembrane $Ca^{2+}-current\;and\;Ca^{2+}$release from the SR.

• 대한약리학회지
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• 제30권1호
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• pp.67-73
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• 1994

Na-Ca 교환은 calcium 이온을, 세포 내외의 Na 이온 농도차에 의해서 형성되는 원동력의 방향에 따라, 세포내로(역방향 Na-Ca 교환), 혹은 세포밖으로(정방향 Na-Ca 교환) 이동시킨다. 그러므로 Na-Ca 교환은 심근 수축 운동의 조절 기전의 하나로 받아 들여지고 있다. 그러나, 세포내의 Na 이온 농도는 항상 세포외의 농도보다 낮으므로, 역방향 Na-Ca 교환의 존재와 아울러 이의 심근 수축에 있어서의 역할 가능성에 대해 많은 연구자들이 회의를 가지고 있는 것이 사실이다. 그러므로 본 연구는 흰쥐의 좌심방을 이용하여, 역방향 Na-Ca 교환의 존재 여부와 그 역할의 존재 가능성을 추구하여 보고자 하였다. 흰쥐의 좌심방은 전기장 자극(0.5msec, supramaximal voltage)으로 수축을 유발하고, 자극 빈도를 안정시 4Hz에서 0.4, 1, 8Hz로 변동시킬때 그 수축 장력에서 특징적인 역 사다리 효과(negative staircase effect)가 나타내었으나, 이때 $^{45}Ca$ 섭취는 저빈도로 갈수록, 또한 고빈도로 갈수록 증가되는 이원적인 증가를 나타내었다 자극 빈도를 4Hz 에서 0.4Hz로 변동시에는 수축 장력이 특징적인 삼단계 변환, 즉 급격히 증가하는 첫단계에 이어 급격하게 감소하는 이단계와 안정되어지는 삼단계로 나타났다. $^{45}Ca$ 섭취도 장력 변동과 같은 양상으로 처음 30초 동안에 현저하게 증가한 후 감소되었다. Na-Ca 억제 약물인 benzamil은 $10^{-5}M$에서부터 $3{\times}10^{-4}M$까지 용량에 비례하여 특히 초기의 장력증가를 봉쇄하였다. Bay K-8644$(3{\times}10^{-5}M)$ 처치는 자극 빈도 감소에 따른 수축력 증가를 현저하게 항진시켰으며, benzamil처치는 이때에도 억압을 나타내었다. Verapamil $3{\times}10^{-5}M$ 전처치시에는 4Hz 자극시의 수축 운동은 완전히 소실시켰으나, 0.4 혹은 1 Hz로 바꿈에 따라 수축 운동이 재현되었다. 이때 $^{45}Ca$ 섭취는 verapamil을 전처치하지 않은 경우보다 현저하게 항진되었다. 이상의 결과로 보아, 흰쥐의 좌심방에서 자극 빈도 감소후에는, 먼저 역방향 Na-Ca 교환에 의해 calcium이온이 세포내로 유입되어 수축운동의 항진이 유발되고, 이어 Na-Ca 교환이 정방향으로 변환되어 calcium이온을 세포밖으로 유출시킴에 따라 수축 운동이 감소된다고 생각한다.

• The Korean Journal of Physiology
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• 제18권1호
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• pp.9-17
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• 1984

The second inward current $(i_{si})$ was studied by the two microelectrode voltage clamp technique in the sino-atrial node of the rabbit. The slow component $(i_{si,2})$ of the second inward current was sometimes identified and $i_{si}$ behaved as if it were a mixture of two currents. We analysed the $(i_{si,2})$ in relation to membrane potential and frequency of voltage clamp pulses. 1) Membrane was held at -40mV which was usually found to be zero current level. When depolarizing pulses were applied, the slow inward current $(i_{si})$ was activated. 2) It was shown that there are three categories of the $i_{si}$ activation by the low level of depolarizing clamp pulses. Moderately fast inward current with single component was developed in most cases in the presence of tetrodotoxin(TTX). But sometimes there was two separate components of $i_{si}$ activation in the peak level and the time course. Thirdly the only slow component of $i_{si}$ was found in rare cases. 3) The activation of $(i_{si,2})$ was dependent upon membrane potential. The $i_{si}$ shows two separate peaks during clamp depolarizations and higher clamp pulses lead to fusion of the peaks. 4) The $i_{si,2}$ activation showed that it decreased with repetitive clamp pulses and it was more evident in higher frequencies(2Hz)(negative staircase).