5-Hydroxytryptamine enhances L-type calcium current in norepinephrine-induced hypertrophic ventricular myocytes

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

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.

(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).

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.