Neuropeptide Y increases 4-aminopyridine-sensitive transient outward potassium current in rat ventricular myocytes

1 The modulation of 4-aminopyridine sensitive transient outward potassium current (4-AP I-to) by neuropeptide Y (NPY) (100 nM) in rat ventricular myocytes was examined using the whole cell voltage-clamp technique. 2 Continuous exposure to NPY (100 nM) for 3 - 6 h significantly increased 4-AP I-to density. The stimulation of 4-AP I-to density by NPY was concentration-dependent (EC50 = 10 nM). 3 In the presence of BIBP 3226, an NPY receptor antagonist that binds selectively to NPY Y1-receptors, the effect of NPY on 4-AP Ito density was maintained. However, in the presence of BIIE 0246, a highly selective non-peptide NPY Y2-receptor antagonist, NPY was unable to increase 4-AP I-to density. 4 The effect of NPY on 4-AP I-to. density was prevented by pretreatment with 500 ng ml(-1) pertussis toxin (PTX) and by the specific protein kinase C (PKC) inhibitor, calphostin C (100 nM). 5 Thus, short term exposure to NPY induces an increase of 4-AP Ito density in rat ventricular myocytes mediated by Y2-receptors and involving the action of PKC via a PTX-sensitive signalling cascade.