Chronic levothyroxin treatment is associated with ion channel abnormalities in cardiac and neuronal cells.
1. We investigated the ion currents responsible for repolarization of guinea-pig isolated myocytes (ICa) and rat hippocampal CA1 neurons (IA and IK) by means of the whole-cell holding technique. 2. The rat hypertrophied heart, induced by levothyroxin, caused exaggerated cardiac arrhythmias after coronary ischaemia-reperfusion. 3. We found an enhanced ICa in guinea-pig isolated myocytes and decreased IA and IK in rat hippocampal CA1 neurons following levothyroxin treatment. Blockade of the outward K+ current and an increment in inward Ca2+ current by chronic levothyroxin treatment contributed to the delayed repolarization and aggravated cardiac arrhythmias. 4. Animals treated with chronic levothyroxin may serve as pathological models for the investigation of the pattern of ion channel disorders with regard to impaired repolarization and aggravated cardiac arrhythmias.
Dai
D Z
DZ
Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China. njpdaidz@jlonline.com
Hu
H J
HJ
Yang
D M
DM
Hao
X M
XM
Zhang
G Q
GQ
Zhou
P A
PA
Wu
C H
CH
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000633:toxicity*
D020747:Calcium Channels, T-Type; D007473:Ion Channels; D015221:Potassium Channels; D013974:Thyroxine