Neuropeptide Y contributes to innervation-dependent increase in I(Ca, L) via ventricular Y2 receptors.
The developmental increase in L-type Ca current (I(Ca,L)) density in the rat ventricle is reproduced in vitro by culturing neonatal myocytes with sympathetic neurons. We tested whether this effect of sympathetic innervation results from a chronic or sustained action of neurally released neuropeptide Y (NPY). Ventricular myocytes from newborn rats were cultured in serum-free medium with or without sympathetic neurons, NPY, or NPY analogs. Ca currents were measured in single myocytes at room temperature using the perforated patch clamp. In all cell groups (control, innervated, or NPY treated), the current-voltage relation for I(Ca,L) was represented by a bell-shaped curve with maximal value near 0 mV. The current density at 0 mV normalized to that of corresponding mean control values was 1.63 +/- 0.12 and 1.52 +/- 0.16 for innervated and NPY-treated myocytes, respectively. Both groups differed significantly from control (P < 0.05). NPY analogs exhibited the following rank order of effectiveness: NPY >/= NPY-(13-36) >/= PYY >> [Leu31Pro34]NPY, suggesting that the NPY effect occurs via a Y2-receptor subtype. In confirmation, chronic treatment of innervated cultures with a Y2-selective NPY antagonist prevented the innervation-dependent increase in I(Ca,L). These results indicate that sympathetic innervation contributes to the developmental increase in I(Ca,L) via neurally released NPY acting at Y2 receptors on the ventricular myocytes.
Protas
L
L
Department of Pharmacology, Columbia University, New York, New York 10032, USA.
Robinson
R B
RB
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D006352:Heart Ventricles / Q000294:innervation*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D016276:Ventricular Function
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D002118:Calcium