Sympathetic innervation modulates repolarizing K+ currents in rat epicardial myocytes.
During postnatal development, sympathetic innervation of the heart evolves, and repolarization accelerates. Our goal in this study was to test whether sympathetic innervation modulates the ion channels that regulate repolarization. We studied action potentials and repolarizing K+ currents in epicardial myocytes from rats in which sympathetic innervation was accelerated or delayed, respectively, by subcutaneous injection of nerve growth factor (NGF) or NGF antibody (Ab) for the first 15 days of life. A placebo group was included as well. Action potential duration (APD) to 90% repolarization was greater in the Ab (158 +/- 18 ms)-treated than the NGF (106 +/- 10 ms)-treated animals (P < 0.05); the APD at 90% repolarization for the placebo group was intermediate (125 +/- 30 ms). The transient outward (Ito) and inward rectifier (IK1) K+ currents were recorded in freshly dissociated cells using the whole cell patch-clamp technique. Ito was decreased in density at potentials positive to +40 mV in Ab-treated rats when compared with rats treated with NGF (P < 0.05). In addition, the inactivation curve of Ito in Ab-treated rats was shifted 13 mV positive to that of NGF-treated rats. IK1 also decreased in the Ab-treated group compared with the NGF group in the potential ranges of -100 to -90 mV (P < 0.05). However, the channel transcript abundance (RNA) in NGF-, Ab-, or placebo-treated rat hearts did not differ. Our results suggest that sympathetic innervation contributes to the developmental differences in K+ currents and APD postnatally in the rat.
Liu
Q Y
QY
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York 10032, USA.
Rosen
M R
MR
McKinnon
D
D
Robinson
R B
RB
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D006352:Heart Ventricles / Q000166:cytology / Q000294:innervation*; D008564:Membrane Potentials; D009414:Nerve Growth Factors / Q000502:physiology*; D010496:Pericardium / Q000166:cytology; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013564:Sympathetic Nervous System / Q000502:physiology*
D009414:Nerve Growth Factors; D015221:Potassium Channels; D012333:RNA, Messenger; D015761:4-Aminopyridine