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 (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.
Heredia
M P
MP
Institute of Pharmacology and Toxicology (CSIC-UCM), School of Medicine, Universidad Complutense, 28040 Madrid, Spain.
Fernández-Velasco
M
M
Benito
G
G
Delgado
C
C
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009478:Neuropeptide Y / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D016276:Ventricular Function
D009478:Neuropeptide Y; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D017476:Receptors, Neuropeptide Y; D015761:4-Aminopyridine; D019204:GTP-Binding Proteins