The Guanylyl Cyclase Activator YC-1 Directly Inhibits the Voltage-Dependent K^+ Channels in Rabbit Coronary Arterial Smooth Muscle Cells
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概要
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We investigated the effects of YC-1, an activator of soluble guanylyl cyclase (sGC), on voltage-dependent K+ (Kv) channels in smooth muscle cells from freshly isolated rabbit coronary arteries by using the whole-cell patch clamp technique. YC-1 inhibited the Kv current in a dose-dependent fashion with an apparent Kd of 9.67 μM. It accelerated the decay rate of Kv channel inactivation without altering the kinetics of current activation. The rate constants of association and dissociation for YC-1 were 0.36 ± 0.01 μM−1−1 and 3.44 ± 0.22 s−1, respectively. YC-1 did not have a significant effect on the steady-state activation and inactivation curves. The recovery time constant from inactivation was decreased in the presence of YC-1, and application of train pulses (1 or 2 Hz) caused a progressive increase in the YC-1 blockade, indicating that YC-1–induced inhibition of Kv currents is use-dependent. Pretreatment with Bay 41-2272 (also a sGC activator), ODQ (a sGC inhibitor), or Rp-8-Br-PET-cGMPs (a protein kinase G inhibitor) did not affect the basal Kv current and also did not significantly alter the inhibitory effect of YC-1. From these results, we suggest that YC-1 directly inhibits the Kv current independently of sGC activation and in a state-, time-, and use-dependent fashion.
- 社団法人 日本薬理学会の論文
- 2010-01-20
著者
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Park Yeong-min
Dep. Of Microbiology And Immunology And National Res. Lab. Of Dendritic Cell Differentiation & R
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PARK Yeong-Min
Department of Microbiology & Immunology, and National Research Laboratory of Dendritic Cell Differen
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Han Jin
Department Of Physiology College Of Medicine Inje University
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Park Won
Department Of Physiology College Of Medicine Kwangwon National University
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Ko Eun
Department Of Physiology College Of Medicine Inje University
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KO Eun
National Research Laboratory for Mitochondrial Signaling, FIRST Mitochondria Research Group, Departm
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HAN Jin
National Research Laboratory for Mitochondrial Signaling, FIRST Mitochondria Research Group, Departm
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JUNG In
Department of Microbiology and Immunology and National Research Laboratory of Dentritic, Cell Differ
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PARK Won
National Research Laboratory for Mitochondrial Signaling, FIRST Mitochondria Research Group, Departm
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Ko Jae-Hong
Department of Physiology, College of Medicine, Chung-Ang University, Korea
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Son Youn
Université Paris-Sud 11, Faculté de Pharmacie, France
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Hong Da
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medic
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Choi Tae-Hoon
Department of Physical Education, Andong Science College, Korea
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Kim Nari
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medic
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Jung In
Dep. Of Microbiology And Immunology And National Res. Lab. Of Dendritic Cell Differentiation & R
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Choi Tae-hoon
Department Of Mechanical Engineering Kyungpook National University
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Park Won
National Cri Center For Semiconductor Nanorods And Department Of Materials Science And Engineering
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Kim Nari
National Res. Lab. For Mitochondrial Signaling Dep. Of Physiology Coll. Of Medicine Cardiovascular A
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Ko Jae-hong
Department Of Physiology College Of Medicine Chung-ang University
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Kim Nari
National Research Laboratory For Mitochondrial Signaling Department Of Physiology College Of Medicin
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Choi Tae-hoon
Department Of Physical Education Andong Science College
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Jung In
Department Of Microbiology And Immunology And National Research Laboratory Of Dendritic Cell Differe
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Ko Eun
National Research Laboratory For Mitochondrial Signaling Department Of Physiology College Of Medicin
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Hong Da
National Research Laboratory For Mitochondrial Signaling Department Of Physiology College Of Medicin
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Han Jin
National Research Laboratory For Mitochondrial Signaling Department Of Physiology College Of Medicin
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Son Youn
Universite Paris-sud 11 Faculte De Pharmacie
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Park Young-mi
Department Of Microbiology And Immunology And National Research Laboratory Of Dendritic Cell Differe
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Choi Tae-Hoon
Department of Electronics Engineering, Pusan National University, Busan 609-735, Korea.
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