| 3 | Protriptyline,a tricyclic antidepressant,inhibits voltage-dependent K+channels in rabbit coronary arterial smooth muscle cells显示文摘In this study,we explore the inhibitory effects of protriptyline,a tricyclic antidepressant drug,on voltage-dependent K+(Kv)channels of rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique,Protriptyline inhibited the vascular Kv current in a concentrationdependent manner,with an IC5o value of 5.05±0.97μM and a Hill coefficient of 0.73+0.04.Protriptyline did not affect the steady-state activation kinetics.However,the drug shifted the steadystate inactivation curve to the left,suggesting that protriptyline inhibited the Kv channels by changing their voltage sensitivity.Application of 20 repetitive train pulses(1 or 2 Hz)progressively increased the protriptyline-induced inhibition of the Kv current,suggesting that protriptyline inhibited Kv channels in a use(state)-dependent manner.The extent of Kv current inhibition by protriptyline was similar during the first,second,and third step pulses.These results suggest that protriptyline-induced inhibition of the Kv current mainly occurs principally in the closed state.The increase in the inactivation recovery time constant in the presence of protriptyline also supported use(state)-dependent inhibition of Kv channels by the drug.In the presence of the Kv1.5 inhibitor,protriptyline did not induce further inhibition of the Kv channels.However,pretreatment with a Kv2.1 or Kv7 inhibitor induced further inhibition of Kv current to a similar extent to that observed with protriptyiine alone.Thus,we conclude that protriptyline inhibits the vascular Kv channels in a concentration-and use-dependent manner by changing their gating properties.Furthermore,protriptyline-induced inhibition of Kv channels mainly involves the Kv1.5. | Jin Ryeol An Hojung Kang Hongliang Li Mi Seon Seo Hee Seok Jung Won-Kyo Jung II-Whan Choi Sook Won Ryu Hongzoo Park Young Min Bae Se Min Ryu Won Sun Park | 2020 | Acta Biochimica et Biophysica Sinica2020，52，3： | 0 |
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