Effects of neuropeptide Y on ion channels in ventricular myocytes

Neuropeptide Y (NPY) co-exists with norepinephrine (NE) in sympathetic terminals,and is the most abundant neuropeptide in myocardium.Many studies have focused on the effects of NE on ion channels in cardiac myocytes and its physiological significance has been elucidated relatively profoundly.There have been few investigations,however,on the physiological significance of NPY in myocardium.The effects of NPY on L-type Ca~(2+) channel currents (I_(Ca-L)) were evaluated in some studies and different results were presented,which might be attributed to the different species of animal tested and different methods used.It is necessary,therefore,to study the effects of NPY on ion channels in cardiac myocytes systematically and further to discuss the biological significance of their coexistence with NE in sympathetic terminals.The single ventricular myocytes from adult rat or guinea pig (only for measuring I_K) were prepared using enzymatic dispersion.I_(Ca-L),I_(to),I_(Na/Ca),I_(Na) and I_K in the cellular membrane were observed using whole cell voltage-clamp recording.In the present study,NPY from 1.0 to 100 nmol/L dose-dependently inhibited I_(Ca-L) (P＜0.01,n=5).The maximal rate of inhibition in this study reached 39% and IC_(50) was 1.86 nmol/L.NPY had no effect on the voltage-dependence of calcium current amplitude and on the voltage-dependence of the steady-state gating variables,I_(Ca-L) was activated at -30 mV,reaching the maximum at 0 mV.When both NE and NPY were applied with a concentration ratio of 500:1,10 nmol/L NPY inhibited I_(Ca-L) that had been increased by 5μmol/ L NE,which was consistent with the effect of NPY only on I_(Ca-L).NPY also inhibited I_(Na/Ca).At a concentration of 10 nmol/L,NPY inhibited inward and outward I_(Na/Ca) from (0.27±0.11) pA/pF and (0.45±0.12) pA/pF to (0.06±0.01) pA/pF and (0.27±0.09) pA/pF, respectively (P＜0.05,n=4).NPY at 10 nmol/L increased I_(to) from (12.5±0.70) pA/pF to (14.7±0.59) pA/pF (P＜0.05,n=4).NPY at 10 nmol/L did not affect I_(Na) in rat myocytes and I_K in guinea pig myocytes.NPY increased the speed of action potential depolarization and reduced action potential duration of I_(Ca-L),I_(Na/Ca) and I_(to),which contributed to the reduction of contraction.These results indicate that the effects of NPY are opposite to the effects of NE on ion channels of cardiac myocytes.