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Heredia MP, Fernandez-Velasco M, Benito G, Delgado C: Neuropeptide Y increases 4-aminopyridine-sensitive transient outward potassium current in rat ventricular myocytes. Br J Pharmacol. 2002 Apr;135(7):1701-6.
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 (EC (50)=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 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. 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 I (to) density in rat ventricular myocytes mediated by Y2-receptors and involving the action of PKC via a PTX-sensitive signalling cascade. |
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