Inhibitory effects of serotonin on transient outward potassium current in rat ventricular myocytes.
OBJECTIVE
To study the effects of serotonin (5-hydroxy-tryptamine, 5-HT) on transient outward potassium current (I(to)) and elucidate its mechanism in rat ventricular myocytes.


METHODS
I(to) was recorded using the conventional whole cell patch-clamp techniques.


RESULTS
I(to) density in normal myocytes was similar to that in norepinephrine-induced hypertrophic myocytes. 5-HT depressed I(to) in a concentration-dependent manner with the half-maximal inhibitory concentration of (40+/-5) micromol/L and (38+/-7) micromol/L in normal and hypertrophic ventricular myocytes respectively. Mianserin (5-HT2 receptor antagonist), compound 48/80 (phospholipase C antagonist), and chelerythrine chloride (protein kinase C antagonist) reversed the inhibitory effects of 5-HT on I(to), while phorbol 12-myristate 13-acetate (protein kinase C agonist) enhanced the inhibitory effect of 5-HT on I(to) in normal myocytes.


CONCLUSIONS
5-HT markedly inhibits I(to) in rat ventricular myocytes. The putative signal pathway is that 5-HT activates phospholipase C, which causes inositol phospholipid hydrolysis. The activation of downstream signal molecule, protein kinase C, phosphorates substrate target proteins, which leads to inhibition of I(to) in ventricular myocytes.
Zhao
Ming-Gao
MG
Department of Pharmacology, The Fourth Military Medical University, Xi-an 710032, China. mgzhao@hotmail.com
Mei
Qi-Bing
QB
Zhang
Yan-Feng
YF
Xing
Bing
B
Li
Xiao-Qiang
XQ
Cui
Yi
Y
D000818:Animals; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology*; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*
D015221:Potassium Channels; D012701:Serotonin