• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.731-739
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• 1997

The aim of present study is to investigate the effects of cGMP on hyperpolarization activated inward current ($I_f$), pacemaker current of the heart, in rabbit sino-atrial node cells using the whole-cell patch clamp technique. When sodium nitroprusside (SNP, $80{\mu}M$), which is known to activate guanylyl cyclase, was added, $I_f$ amplitude was increased and its activation was accelerated. However, when $I_f$ was prestimulated by isopreterenol (ISO, $1{\mu}M$), SNP reversed the effect of ISO. In the absence of ISO, SNP shifted activation curve rightward. On the contrary in the presence of ISO, SNP shifted activation curve in opposite direction. $8Br-cGMP(100\;{\mu}M)$, more potent PKG activator and worse PDE activator than cGMP, also increased basal $I_f$ but did not reverse stimulatory effect of ISO. It was probable that PKG activation seemed to be involved in SNP-induced basal $I_f$ increase. The fact that SNP inhibited ISO-stimulated $I_f$ suggested cGMP antagonize cAMP action via the activation of PDE. This possibility was supported by experiment using 3-isobutyl-1-methylxanthine (IBMX), non-specific PDE inhibitor. SNP did not affect $I_f$ when $I_f$ was stimulated by $20{\mu}M$ IBMX. Therefore, cGMP reversed the stimulatory effect of cAMP via cAMP breakdown by activating cGMP-stimulated PDE. These results suggest that PKG and PDE are involved in the modulation of $I_f$ by cGMP: PKG may facilitate $I_f$ and cGMP-stimulated PDE can counteract the stimulatory action of cAMP.

• The Korean Journal of Physiology
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• 제17권1호
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• pp.1-11
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• 1983

1) 토끼동방결절의 작은 절편에 미세 전극 두개로 voltage clamp를 하고 과분극에 의하여 활성화되는 내향전류, $i_f$의 동력학적 성상을 분석하였다. 2) 전류 $i_f$는 $10^{-7}g/ml$ TTX와 2 mM $Mn^{2+}$의 존재하에서 과분극 pulse에 의하여 활성화되었으며 그 범위는 $-45\;mV{\sim}-75\;mV$였다. 전류의 크기와 시간경과는 막전압이 과분극될수록 커지고 빨라졌다. 3) Envelope test결과 $i_f$전류는 단일 gate에 의하여 지수합수적 (exponential)으로 조절됨을 보였다. 4) 2 mM의 $Ba^{2+}$에 의하여$i_f$전류의 크기는 감소하고 시간경과도 느려졌으며 반응속도상수와 gating molecule의 열리고 닫히는 반응계수(rate coefficient; ${\alpha}_s$, ${\beta}_s$)와 막전압 관계곡선을 과분극쪽으로 이동시켰다. 이러한 $Ba^{2+}$의 효과는 24 mM $K^+$에 의하여 일부 상쇄되었다.