The Guanylyl Cyclase Activator YC-1 Directly Inhibitsthe Voltage-Dependent K+ Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Journal of Pharmacological Sciences

Jin Han⁴  Eun A Ko⁴  Won Sun Park⁴  Youn Kyoung Son³  Da Hye Hong⁴  Jae-Hong Ko¹  Tae-Hoon Choi⁵  Yeong-Min Park²  In Duk Jung²  Nari Kim⁴ 

[1] Department of Physiology, College of Medicine, Chung-Ang University, Korea;Department of Microbiology and Immunology and National Research Laboratory of Dendritic Cell Differentiation & Regulation, Medical Research Institute, Pusan National University, College of Medicine, Korea;Université Paris-Sud 11, Faculté de Pharmacie, France;National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, FIRST Mitochondrial Research Group, Biomarker Medical Research Center, Inje University, Korea;Department of Physical Education, Andong Science College, Korea

关键词: YC-1;    voltage-dependent K+ channel;    guanylyl cyclase;    coronary artery;   

DOI  :  10.1254/jphs.09228FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(43)Cited-By(12)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·s−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.

【 授权许可】

Unknown