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Selective serotonin reuptake inhibitor sertraline inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

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Abstract

We examined the effects of the selective serotonin reuptake inhibitor (SSRI) sertraline on voltage-dependent K+ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using the voltage-clamp technique. Sertraline decreased the Kv channel current in a dose-dependent manner, with an IC50 value of 0.18 μM and a slope value (Hill coefficient) of 0.61. Although the application of 1 μM sertraline did not affect the steady-state activation curves, sertraline caused a significant, negative shift in the inactivation curves. Pretreatment with another SSRI, paroxetine, had no significant effect on Kv currents and did not alter the inhibitory effects of sertraline on Kv currents. From these results, we concluded that sertraline dose-dependently inhibited Kv currents independently of serotonin reuptake inhibition by shifting inactivation curves to a more negative potential.

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References

  • Bae YM, Kim A, Kim J, Park SW, Kim TK, Lee YR, Kim B and Cho SI 2006 Serotonin depolarizes the membrane potential in rat mesenteric artery myocytes by decreasing voltage-gated K+ currents. Biochem. Biophys. Res. Commun. 347 468–476

    Article  CAS  PubMed  Google Scholar 

  • Edwards JG and Anderson I 1999 Systematic review and guide to selection of selective serotonin reuptake inhibitors. Drugs. 57 507–533

    Article  CAS  PubMed  Google Scholar 

  • Hong DH, Choi IW, Son YK, Kim DJ, Na SH, Jung WK, Yoon YW and Park WS 2013 The effect of P13 kinase inhibitor LY294002 on voltage-dependent K(+) channels in rabbit coronary arterial smooth muscle cells. Life Sci. 92 916–922

    Article  CAS  PubMed  Google Scholar 

  • Hong DH, Li H, Kim HS, Kim HW, Shin SE, Jung WK, Na SH, Choi IW, et al. 2015 The effects of the selective serotonin reuptake inhibitor fluvoxamine on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. Biol. Pharm. Bull. 38 1208–1213

    Article  CAS  PubMed  Google Scholar 

  • Hong DH, Son YK, Li H, Jung ID, Park YM, Jung WK, Kim HS, Choi IW, et al. 2014 The calmodulin inhibitor and antipsychotic drug trifluoperazine inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. Biochem. Biophys. Res. Commun. 443 321–425

    Article  CAS  PubMed  Google Scholar 

  • Hong DH, Yang D, Choi IW, Son YK, Jung WK, Kim DJ, Han J, Na SH, et al. 2012 The T-type Ca2+ channel inhibitor mibefradil inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. J. Pharmacol. Sci. 120 196–205

    Article  CAS  PubMed  Google Scholar 

  • Ko EA, Park WS, Firth AL, Kim N, Yuan JX and Han J 2010a Pathophysiology of voltage-gated K+ channels in vascular smooth muscle cells: modulation by protein kinases. Prog. Biophys. Mol. Biol. 103 95–101

    Article  CAS  PubMed  Google Scholar 

  • Ko EA, Park WS, Son YK, Kim DH, Kim N, Kim HK, Choi TH, Jung ID, et al. 2009 The effect of tyrosine kinase inhibitor genistein on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. Vasc. Pharmacol. 50 51–56

    Article  CAS  Google Scholar 

  • Ko EA, Park WS, Son YK, Ko JH, Choi TH, Jung ID, Park YM, Hong DH, et al. 2010b Calcium channel inhibitor, verapamil, inhibits the voltage-dependent K+ channels in rabbit coronary smooth muscle cells. Biol. Pharm. Bull. 33 47–52

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi T, Washiyama K and Ikeda K 2011 Inhibition of G protein-activated inwardly rectifying K+ channels by different classes of antidepressants. PLoS ONE. 6, e28208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee HA, Kim KS, Hyun SA, Park SG and Kim SJ 2012 Wide spectrum of inhibitory effects of sertraline on cardiac ion channels. Korean J. Physiol. Pharmacol. 16 327–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Choi IW, Hong DH, Son YK, Na SH, Jung WK, Firth AL, Jung ID, et al. 2015a W-7 inhibits voltage-dependent K+ channels independent of calmodulin activity in rabbit coronary arterial smooth muscle cells. Eur. J. Pharmacol. 750C 14–19

    Article  Google Scholar 

  • Li H, Hong DH, Kim HS, Kim HW, Jung WK, Na SH, Jung ID, Park YM, et al. 2015b The calmodulin inhibitor CGS 9343B inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. Toxicol. Appl. Pharmacol. 15 207–213

    Article  CAS  Google Scholar 

  • Maertens C, Droogmans G, Verbesselt R and Nilius B 2002 Block of volume-regulated anion channels by selective serotonin reuptake inhibitors. Naunyn Schmiedebergs Arch. Pharmacol. 366 158–165

    Article  CAS  PubMed  Google Scholar 

  • Mann JJ 2005 The management of depression. N. Engl. J. Med. 353 1819–1834

    Article  CAS  PubMed  Google Scholar 

  • Meijer WE, Heerdink ER, Leufkens HG, Herings RM, Egberts AC and Nolen WA 2004 Incidence and determinants of long-term use of antidepressants. Eur. J. Clin. Pharmacol. 60 57–61

    Article  PubMed  Google Scholar 

  • Nelson MT and Quayle JM 1995 Physiological roles and properties of potassium channels in arterial smooth muscle. Am. J. Physiol. 268 799–822

    Google Scholar 

  • Ninan PT 2003 Obsessive-compulsive disorder: implication of the efficacy of an SSRI, paroxetine. Psychopharmacol. Bull. 37 89–96

    PubMed  Google Scholar 

  • Ohno Y, Hibino H, Lossin C, Inanobe A and Kurachi Y 2007 Inhibition of astroglial Kir4.1 channels by selective serotonin reuptake inhibitors. Brain Res. 1178 44–51

    Article  CAS  PubMed  Google Scholar 

  • Owens MJ, Morgan WN, Plott SJ and Nemeroff CB 1997 Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J. Pharmacol. Exp. Ther. 283 1305–1322

    CAS  PubMed  Google Scholar 

  • Park MH, Son YK, Hong DH, Choi IW, Kim DJ, Lee H, Bang H, Na SH, et al. 2013 The Ca2+ channel inhibitor efonidipine decreases voltage-dependent K+ channel activity in rabbit coronary arterial smooth muscle cells. Vasc. Pharmacol. 59 90–95

    Article  CAS  Google Scholar 

  • Park WS, Han J, Kim N, Ko JH, Kim SJ and Earm Y 2005a Activation of inward rectifier K+ channels by hypoxia in rabbit coronary arterial smooth muscle cells. Am. J. Physiol. 289 H2461–H2467

    CAS  Google Scholar 

  • Park WS, Ko JH, Ko EA, Son YK, Hong DH, Jung ID, Park YM, Choi TH, et al. 2010 The guanylyl cyclase activator YC-1 directly inhibits the voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. J. Pharmacol. Sci. 112 64–72

    Article  CAS  PubMed  Google Scholar 

  • Park WS, Son YK, Han J, Kim N, Ko JH, Bae YM and Earm YE 2005b Staurosporine inhibits voltage-dependent K+ current through a PKC-independent mechanism in isolated coronary arterial smooth muscle cells. J. Cardiovasc. Pharmacol. 45 260–269

    Article  CAS  PubMed  Google Scholar 

  • Park WS, Son YK, Ko EA, Ko JH, Lee HA, Park KS and Earm YE 2005c The protein kinase C inhibitor, bisindolylmaleimide (I), inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells. Life Sci. 77 512–527

    Article  CAS  PubMed  Google Scholar 

  • Shank RP, Vaught JL, Pelley KA, Setler PE, McComesey DF and Maryanoff BE 1988 McN-5652: a highly potent inhibitor of serotonin uptake. J. Pharmacol. Exp. Ther. 247 1032–1038

    CAS  PubMed  Google Scholar 

  • Sheehan DV and Kamijima K 2009 An evidence-based review of the clinical use of sertraline in mood and anxiety disorders. Int. Clin. Psychopharmacol. 24 43–60

    Article  PubMed  Google Scholar 

  • Shimoda LA, Sylvester JT and Sham JS 1998 Inhibition of voltage-dependent K+ current in rat intrapulmonary arterial myocytes by endothelin-1. Am. J. Physiol. 274 842–853

    Google Scholar 

  • Snyders DJ and Yeola SW 1995 Determinants of antiarrhythmic drug action. electrostatic and hydrophobic components of block of the human cardiac hKv1.5 channel. Circ. Res. 77 575–583

    Article  CAS  PubMed  Google Scholar 

  • Son YK, Hong DH, Li H, Kim DJ, Na SH, Park H, Jung WK, Choi IW, et al. 2014 The Ca2+ channel inhibitor NNC 55-0396 inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. J. Pharmacol. Sci. 19 312–319

    Article  Google Scholar 

  • Son YK, Park WS, Kim SJ, Earm YE, Kim N, Youm JB, Warda M, Kim E, et al. 2006 Direct inhibition of a PKA inhibitor, H-89 on Kv channels in rabbit coronary arterial smooth muscle cells. Biochem. Biophys. Res. Commun. 341 931–937

    Article  CAS  PubMed  Google Scholar 

  • Wang GK, Mitchell J and Wang SY 2008 Block of persistent late Na+ currents by antidepressant sertraline and paroxetine. J. Membr. Biol. 222 79–90

    Article  CAS  PubMed  Google Scholar 

  • Watts SW 2005 5-HT in systemic hypertension: foe, friend or fantasy? Clin. Sci. (Lond.). 108 399–412

    Article  CAS  Google Scholar 

  • Yuan XJ 1995 Voltage-gated Kv currents regulate resting membrane potential and [Ca2+]i in pulmonary arterial myocytes. Circ. Res. 77 370–378

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Education: 2014-R1A1A4A01003840) (Ministry of Science, ICT and Future Planning: 2012-M3A9C7050184). This study was also supported by 2015 Research Grant from Kangwon National University (No. 520150339).

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Correspondence to Won Sun Park.

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Corresponding editor: Neeraj Jain

[Kim HS, Li H, Kim HW, Shin SE, Choi I-W, Firth AL, Bang H, Bae YM and Park WS 2016 Selective serotonin reuptake inhibitor sertraline inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. J. Biosci.]

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Kim, H.S., Li, H., Kim, H.W. et al. Selective serotonin reuptake inhibitor sertraline inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. J Biosci 41, 659–666 (2016). https://doi.org/10.1007/s12038-016-9645-6

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