동방결절에서 과분극에 의해 활성화되는 내향전류에 대한 Cyclic-GMP의 영향

• 영문명: Effects of Cyclic-GMP on Hyperpolarization-activated inward Current (If) in Sino-atrial Node Cells of Rabbit
• 발행기관: 대한생리학회-대한약리학회
• 저자명: 유신(Shin Yoo) 호원경(Won Kyung Ho) 엄융의(Yung E Earm)
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제1권 제6호, 731~739쪽, 전체 9쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 1997.01.01

영문 초록

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, 80μM), 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, 1μM), 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 μM), 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 20μM 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.

키워드

Sino-atrial node Hyperpolarization-activated inward current(I_f) cGMP cAMP IBMX