PMID- 23922993
OWN - NLM
STAT- MEDLINE
DCOM- 20140821
LR  - 20240320
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 7
DP  - 2013
TI  - Amiodarone inhibits apamin-sensitive potassium currents.
PG  - e70450
LID - 10.1371/journal.pone.0070450 [doi]
LID - e70450
AB  - BACKGROUND: Apamin sensitive potassium current (I KAS), carried by the type 2 
      small conductance Ca(2+)-activated potassium (SK2) channels, plays an important 
      role in post-shock action potential duration (APD) shortening and recurrent 
      spontaneous ventricular fibrillation (VF) in failing ventricles. OBJECTIVE: To 
      test the hypothesis that amiodarone inhibits I KAS in human embryonic kidney 293 
      (HEK-293) cells. METHODS: We used the patch-clamp technique to study I KAS in 
      HEK-293 cells transiently expressing human SK2 before and after amiodarone 
      administration. RESULTS: Amiodarone inhibited IKAS in a dose-dependent manner 
      (IC50, 2.67 +/- 0.25 microM with 1 microM intrapipette Ca(2+)). Maximal inhibition was 
      observed with 50 microM amiodarone which inhibited 85.6 +/- 3.1% of IKAS induced with 1 
      microM intrapipette Ca(2+) (n = 3). IKAS inhibition by amiodarone was not 
      voltage-dependent, but was Ca(2+)-dependent: 30 microM amiodarone inhibited 81.5+/-1.9% 
      of I KAS induced with 1 microM Ca(2+) (n = 4), and 16.4+/-4.9% with 250 nM Ca(2+) 
      (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts 
      voltage-independent but Ca(2+) dependent inhibition of I KAS. CONCLUSION: Both 
      amiodarone and desethylamiodarone inhibit I KAS at therapeutic concentrations. 
      The inhibition is independent of time and voltage, but is dependent on the 
      intracellular Ca(2+) concentration. SK2 current inhibition may in part underlie 
      amiodarone's effects in preventing electrical storm in failing ventricles.
FAU - Turker, Isik
AU  - Turker I
AD  - Krannert Institute of Cardiology and Division of Cardiology, Department of 
      Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
FAU - Yu, Chih-Chieh
AU  - Yu CC
FAU - Chang, Po-Cheng
AU  - Chang PC
FAU - Chen, Zhenhui
AU  - Chen Z
FAU - Sohma, Yoshiro
AU  - Sohma Y
FAU - Lin, Shien-Fong
AU  - Lin SF
FAU - Chen, Peng-Sheng
AU  - Chen PS
FAU - Ai, Tomohiko
AU  - Ai T
LA  - eng
GR  - R01HL78932/HL/NHLBI NIH HHS/United States
GR  - P01 HL078931/HL/NHLBI NIH HHS/United States
GR  - R01HL71140/HL/NHLBI NIH HHS/United States
GR  - P01HL78931/HL/NHLBI NIH HHS/United States
GR  - R01 HL078932/HL/NHLBI NIH HHS/United States
GR  - R01 HL071140/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130729
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (KCNN2 protein, human)
RN  - 0 (Small-Conductance Calcium-Activated Potassium Channels)
RN  - 24345-16-2 (Apamin)
RN  - M31FU99E3Y (desethylamiodarone)
RN  - N3RQ532IUT (Amiodarone)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amiodarone/analogs & derivatives/*pharmacology
MH  - Anti-Arrhythmia Agents/*pharmacology
MH  - Apamin/*pharmacology
MH  - Calcium/metabolism
MH  - Dose-Response Relationship, Drug
MH  - HEK293 Cells
MH  - Humans
MH  - Intracellular Space/metabolism
MH  - Patch-Clamp Techniques
MH  - Small-Conductance Calcium-Activated Potassium Channels/*antagonists & 
      inhibitors/genetics/*metabolism
MH  - Ventricular Fibrillation/metabolism
PMC - PMC3726612
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/08/08 06:00
MHDA- 2014/08/22 06:00
PMCR- 2013/07/29
CRDT- 2013/08/08 06:00
PHST- 2012/09/05 00:00 [received]
PHST- 2013/06/24 00:00 [accepted]
PHST- 2013/08/08 06:00 [entrez]
PHST- 2013/08/08 06:00 [pubmed]
PHST- 2014/08/22 06:00 [medline]
PHST- 2013/07/29 00:00 [pmc-release]
AID - PONE-D-12-26765 [pii]
AID - 10.1371/journal.pone.0070450 [doi]
PST - epublish
SO  - PLoS One. 2013 Jul 29;8(7):e70450. doi: 10.1371/journal.pone.0070450. Print 2013.