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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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