The Guanylyl Cyclase Activator YC-1 Directly Inhibits the Voltage-Dependent K+ Channels in Rabbit Coronary Arterial Smooth Muscle Cellsopen access
- Authors
- Park, Won Sun; Ko, Jae-Hong; Ko, Eun A.; Son, Youn Kyoung; Hong, Da Hye; Jung, In Duk; Park, Yeong-Min; Choi, Tae-Hoon; Kim, Nari; Han, Jin
- Issue Date
- Jan-2010
- Publisher
- JAPANESE PHARMACOLOGICAL SOC
- Keywords
- YC-1; voltage-dependent K+ channel; guanylyl cyclase; coronary artery
- Citation
- JOURNAL OF PHARMACOLOGICAL SCIENCES, v.112, no.1, pp 64 - 72
- Pages
- 9
- Journal Title
- JOURNAL OF PHARMACOLOGICAL SCIENCES
- Volume
- 112
- Number
- 1
- Start Page
- 64
- End Page
- 72
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/22694
- DOI
- 10.1254/jphs.09228FP
- ISSN
- 1347-8613
1347-8648
- Abstract
- 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 K-d of 9.67 mu M. 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 mu M-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.
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