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Sympathetic innervation modulates repolarizing K+ currents in rat epicardial myocytes
Q Y Liu1, M R Rosen, D McKinnon
1Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York 10032, USA.
The American Journal of Physiology
|April 8, 1998
Summary
Sympathetic innervation influences heart repolarization by modulating key potassium (K+) ion channels during development. This study shows nerve growth factor (NGF) impacts action potential duration (APD) and K+ currents in rat hearts.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Neuroscience
Background:
- Sympathetic innervation of the heart develops postnatally, coinciding with accelerated repolarization.
- The role of sympathetic innervation in modulating cardiac ion channels during this critical developmental period is not fully understood.
Purpose of the Study:
- To investigate whether sympathetic innervation modulates the specific ion channels responsible for cardiac repolarization.
- To determine the impact of altered sympathetic innervation on action potential duration (APD) and potassium (K+) currents in developing rat hearts.
Main Methods:
- Epicardial myocytes were isolated from rat pups treated with nerve growth factor (NGF), NGF antibody (Ab), or placebo during the first 15 days of life.
- Action potentials and repolarizing K+ currents (transient outward K+ current [Ito] and inward rectifier K+ current [IK1]) were measured using whole-cell patch-clamp electrophysiology.
- Analysis included action potential duration (APD) and current density, inactivation curves, and channel transcript abundance (RNA).
Main Results:
- APD was significantly longer in Ab-treated rats (delayed innervation) compared to NGF-treated rats (accelerated innervation).
- Ito density was reduced at positive potentials, and its inactivation curve was shifted in Ab-treated rats versus NGF-treated rats.
- IK1 current density was also decreased in Ab-treated rats compared to NGF-treated rats, particularly at negative potentials.
- No significant differences in K+ channel transcript abundance (RNA) were observed between the treatment groups.
Conclusions:
- Sympathetic innervation plays a crucial role in regulating the developmental changes of cardiac K+ currents and action potential duration postnatally in rats.
- While sympathetic innervation affects K+ current function, it does not appear to alter the expression levels of the corresponding channel transcripts during this developmental window.