5-Hydroxytryptamine enhances L-type calcium current in norepinephrine-induced hypertrophic ventricular myocytes.
OBJECTIVE
To study the effects of 5-hydroxytryptamine (5-HT) on L-type calcium current (ICa) in norepinephrine (NE)-induced hypertrophic ventricular myocytes.


METHODS
Left ventricular hypertrophy was induced by injecting NE intraperitoneally in rats. The single myocytes were isolated enzymatically from left ventricle. ICa was recorded with the whole-cell configuration of the patch-cl amp technique.


RESULTS
(1) The ratio of left heart weight to body weight (LHW/BW) was higher (P < 0.01) in the NE-treated rats compared with the control rats on d 15. LHW/BW was increased 31.8 % in NE-treated rats. (2) ICa was larger in hypertrophic cells than that in normal cells (4.5 p A/pF +/- 0.5 pA/pF vs 3.5 pA/pF +/- 0.3 pA/pF, respectively, at testing potential of 0 mV; P < 0.01). (3) 5-HT (1, 10 micromol/L) increased ICa and decreased the peak current potential from 0 mV to -10 mV in both myocytes. The augmentation of ICa induced by 5-HT was larger in hypertrophic ones. (4) 5-HT did not markedly influence the steady-state activation kinetics. However, 5-HT shifted steady-state inactivation curve with half inactivation voltage V 1/2 changing from -39.5 mV +/- 1.8 mV to -27.8 mV +/- 1.7 m V (P < 0.05), while not changing the voltage responsiveness of calcium channel (slope factor k was not changed markedly).


CONCLUSIONS
5 -HT increased ICa in ventricular myocytes by changing the kinetics of steady-st ate inactivation. A larger alteration of ICa induced by 5-HT i n hypertrophic ventricular myocytes suggests that 5-HT be more prone to induce arrhythmia in hypertrophic heart than in normal one.
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
Xiong
Xiao-Yun
XY
Lu
Bao-Hua
BH
Xing
Bin
B
Zhao
De-Hua
DH
D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002469:Cell Separation; D004594:Electrophysiology; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*
D020746:Calcium Channels, L-Type; D012701:Serotonin; D009638:Norepinephrine