title: Ca2+ channel inhibitor NNC 55-0396 inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.
abstract: We demonstrated the inhibitory effect of NNC 55-0396, a T-type Ca(2+) channel inhibitor, on voltage-dependent K(+) (K(V)) channels in freshly isolated rabbit coronary arterial smooth muscle cells. NNC 55-0396 decreased the amplitude of K(V) currents in a concentration-dependent manner, with an IC(50) of 0.080 μM and a Hill coefficient of 0.76.NNC 55-0396 did not affect steady-state activation and inactivation curves, indicating that the compound does not affect the voltage sensitivity of K(V) channel gating. Both the K(V) currents and the inhibitory effect of NNC 55-0396 on K(V) channels were not altered by depletion of extracellular Ca(2+) or intracellular ATP, suggesting that the inhibitory effect of NNC 55-0396 is independent of Ca(2+)-channel activity and phosphorylation-dependent signaling cascades. From these results, we concluded that NNC 55-0396 dosedependently inhibits K(V) currents, independently of Ca(2+)-channel activity and intracellular signaling cascades.
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Korea.
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.forename: Da Hye
authors.initials: DH
authors.lastname: Hong
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.forename: Dae-Joong
authors.initials: DJ
authors.lastname: Kim
authors.forename: Sung Hun
authors.initials: SH
authors.lastname: Na
authors.forename: Hongzoo
authors.initials: H
authors.lastname: Park
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000502:physiology; D020013:Calcium Signaling; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology*; D003521:Cyclopropanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology*; D010766:Phosphorylation; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000502:physiology; D011817:Rabbits
chemical_list: D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D003521:Cyclopropanes; D009281:Naphthalenes; D024642:Potassium Channels, Voltage-Gated; C484287:NNC 55-0396