Inhibitory effects of serotonin on transient outward potassium current in rat ventricular myocytes.
Abstract
AIM: 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.
CONCLUSION: 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.
Keywords:
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.
CONCLUSION: 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.