Abstract

Balance in the body's hormonal axes depends on feedback onto neuroendocrine hypothalamic neurons. This phenomenon involves transcriptional and biosynthetic effects, yet less is known about the potential rapid modulation of electrical properties. Here, we investigated this issue in the lactotrophic axis, in which the pituitary hormone prolactin is tonically inhibited by tuberoinfundibular dopamine (TIDA) neurons located in the hypothalamic arcuate nucleus. Whole-cell recordings were performed on slices of the rat hypothalamus. In the presence of prolactin, spontaneously oscillating TIDA cells depolarized, switched from phasic to tonic discharge, and exhibited broadened action potentials. The underlying prolactin-induced current is composed of separate low- and high-voltage components that include the activation of a transient receptor potential-like current and the inhibition of a Ca(2+)-dependent BK-type K(+) current, respectively, as revealed by ion substitution experiments and pharmacological manipulation. The two components of the prolactin-induced current appear to be mediated through distinct signaling pathways as the high-voltage component is abolished by the phosphoinositide 3-kinase blocker wortmannin, whereas the low-voltage component is not. This first description of the central electrophysiological actions of prolactin suggests a novel feedback mechanism. By simultaneously enhancing the discharge and spike duration of TIDA cells, increased serum prolactin can promote dopamine release to limit its own secretion with implications for the control of lactation, sexual libido, fertility, and body weight.

Links

Publisher Full Text

Authors

Lyons DJ, Hellysaz A, Broberger C

Institution

Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. David.Lyons@ki.se

Source

The Journal of neuroscience : the official journal of the Society for Neuroscience 32:23 2012 Jun 6 pg 8074-83

MeSH

Action Potentials
Animals
Arcuate Nucleus
Boron Compounds
Calcium
Data Interpretation, Statistical
Dopamine
Electrophysiological Phenomena
Feedback, Physiological
Female
Indicators and Reagents
Ion Channels
Lactation
Large-Conductance Calcium-Activated Potassium Channels
Membrane Potentials
Neurons
Patch-Clamp Techniques
Phosphatidylinositol 3-Kinases
Prolactin
Rats
Rats, Sprague-Dawley

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22674282