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

The modulation of 4‐aminopyridine sensitive transient outward potassium current (4‐AP I to ) by neuropeptide Y (NPY) (100 n M ) in rat ventricular myocytes was examined using the whole cell voltage‐clamp technique. Continuous exposure to NPY (100 n M ) for 3 – 6 h significantly increased 4‐AP I to density. The stimulation of 4‐AP I to density by NPY was concentration‐dependent (EC 50 =10 n M ). In the presence of BIBP 3226, an NPY receptor antagonist that binds selectively to NPY Y1‐receptors, the effect of NPY on 4‐AP I to 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. 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 n M ). Thus, short term exposure to NPY induces an increase of 4‐AP I to density in rat ventricular myocytes mediated by Y2‐receptors and involving the action of PKC via a PTX‐sensitive signalling cascade.British Journal of Pharmacology (2002) 135 , 1701–1706; doi: 10.1038/sj.bjp.0704643