title: Apamin does not inhibit human cardiac Na+ current, L-type Ca2+ current or other major K+ currents.
abstract: BACKGROUND
  Apamin is commonly used as a small-conductance Ca2+-activated K+ (SK) current inhibitor. However, the specificity of apamin in cardiac tissues remains unclear.
  
  
  OBJECTIVE
  To test the hypothesis that apamin does not inhibit any major cardiac ion currents.
  
  
  METHODS
  We studied human embryonic kidney (HEK) 293 cells that expressed human voltage-gated Na+, K+ and Ca2+ currents and isolated rabbit ventricular myocytes. Whole-cell patch clamp techniques were used to determine ionic current densities before and after apamin administration.
  
  
  RESULTS
  Ca2+ currents (CACNA1c+CACNB2b) were not affected by apamin (500 nM) (data are presented as median [25th percentile;75th percentile] (from -16 [-20;-10] to -17 [-19;-13] pA/pF, P = NS), but were reduced by nifedipine to -1.6 [-3.2;-1.3] pA/pF (p = 0.008). Na+ currents (SCN5A) were not affected by apamin (from -261 [-282;-145] to -268 [-379;-132] pA/pF, P = NS), but were reduced by flecainide to -57 [-70;-47] pA/pF (p = 0.018). None of the major K+ currents (IKs, IKr, IK1 and Ito) were inhibited by 500 nM of apamin (KCNQ1+KCNE1, from 28 [20]; [37] to 23 [18]; [32] pA/pF; KCNH2+KCNE2, from 28 [24]; [30] to 27 [24]; [29] pA/pF; KCNJ2, from -46 [-48;-40] to -46 [-51;-35] pA/pF; KCND3, from 608 [505;748] to 606 [454;684]). Apamin did not inhibit the INa or ICaL in isolated rabbit ventricular myocytes (INa, from -67 [-75;-59] to -68 [-71;-59] pA/pF; ICaL, from -16 [-17;-14] to -14 [-15;-13] pA/pF, P = NS for both).
  
  
  CONCLUSIONS
  Apamin does not inhibit human cardiac Na+ currents, L-type Ca2+ currents or other major K+ currents. These findings indicate that apamin is a specific SK current inhibitor in hearts as well as in other organs.
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Integrated Diagnostic & Therapeutics, National Taiwan University, Taipei, Taiwan.
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Yu
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Molecular Pathogenesis, Division of Pathophysiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ai
authors.affiliation: Cardiovascular Research Laboratory, Departments of Medicine (Cardiology) and Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000818:Animals; D001030:Apamin / Q000737:chemistry* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D057809:HEK293 Cells; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D017136:Ion Transport; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D061567:Voltage-Gated Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D024642:Potassium Channels, Voltage-Gated; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D001030:Apamin; D002118:Calcium