Regulation of cardiac innervation and function via the p75 neurotrophin receptor

Beth Habecker, Parizad Bilimoria, Camille Linick, Kurt Gritman, Christina U. Lorentz, William Woodward, Susan J. Birren

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Homeostatic regulation of cardiac function is dependent on the balance of inputs from the sympathetic and parasympathetic nervous systems. We investigated whether the p75 neurotrophin receptor plays a developmental role in cardiac innervation by analyzing sympathetic and parasympathetic fibers in the atria of p75 knockout and wildtype mice at several stages of postnatal development, and examining the effect on control of heart rate. We found that parasympathetic innervation of the atria in p75-/- mice was similar to wildtype at all time points, but that the density of sympathetic innervation was dynamically regulated. Compared to wildtype mice, the p75-/- mice had less innervation at postnatal day 4, an increase at day 28, and decreased innervation in adult mice. These changes reflect defects in initial fiber in-growth and the timing of the normal developmental decrease in sympathetic innervation density in the atria. Thus, p75 regulates both the growth and stability of cardiac sympathetic fibers. The distribution of sympathetic fibers was also altered, so that many regions lacked innervation. Basal heart rate was depressed in adult p75-/- mice, and these mice exhibited a diminished heart rate response to restraint stress. This resulted from the lack of sympathetic innervation rather than increased parasympathetic transmission or a direct effect of p75 in cardiac cells. Norepinephrine was elevated in p75-/- atria, but stimulating norepinephrine release with tyramine produced less tachycardia in p75-/- mice than wild type mice. This suggests that altered density and distribution of sympathetic fibers in p75-/- atria impairs the control of heart rate.

Original languageEnglish (US)
Pages (from-to)40-48
Number of pages9
JournalAutonomic Neuroscience: Basic and Clinical
Volume140
Issue number1-2
DOIs
StatePublished - Jun 2008

Fingerprint

Nerve Growth Factor Receptor
Adrenergic Fibers
Heart Rate
Norepinephrine
Parasympathetic Nervous System
Tyramine
Sympathetic Nervous System
Growth
Tachycardia
Knockout Mice

Keywords

  • Autonomic control
  • Axon maintenance
  • Axon outgrowth
  • Development
  • Parasympathetic
  • Sympathetic

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Endocrine and Autonomic Systems

Cite this

Regulation of cardiac innervation and function via the p75 neurotrophin receptor. / Habecker, Beth; Bilimoria, Parizad; Linick, Camille; Gritman, Kurt; Lorentz, Christina U.; Woodward, William; Birren, Susan J.

In: Autonomic Neuroscience: Basic and Clinical, Vol. 140, No. 1-2, 06.2008, p. 40-48.

Research output: Contribution to journalArticle

Habecker, Beth ; Bilimoria, Parizad ; Linick, Camille ; Gritman, Kurt ; Lorentz, Christina U. ; Woodward, William ; Birren, Susan J. / Regulation of cardiac innervation and function via the p75 neurotrophin receptor. In: Autonomic Neuroscience: Basic and Clinical. 2008 ; Vol. 140, No. 1-2. pp. 40-48.
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