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Am J Physiol Heart Circ Physiol 277: H940-H946, 1999;
0363-6135/99 $5.00
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Vol. 277, Issue 3, H940-H946, September 1999

Neuropeptide Y contributes to innervation-dependent increase in ICa,L via ventricular Y2 receptors

Lev Protas and Richard B. Robinson

Department of Pharmacology, Columbia University, New York, New York 10032

The developmental increase in L-type Ca current (ICa,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 ICa,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 ICa,L. These results indicate that sympathetic innervation contributes to the developmental increase in ICa,L via neurally released NPY acting at Y2 receptors on the ventricular myocytes.

sympathetic innervation; neonatal cardiomyocytes; calcium current


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